[{"article_processing_charge":"No","status":"public","main_file_link":[{"open_access":"1","url":"http://wrap.warwick.ac.uk/168325/1/WRAP-denylate-cyclase-activity-TIR1-AFB-auxin-receptors-root-growth-22.pdf"}],"date_created":"2023-01-12T12:06:05Z","acknowledgement":"This research was supported by the Lab Support Facility (LSF) and the Imaging and Optics Facility (IOF) of IST Austria. We thank C. Gehring for suggestions and advice; and K. U. Torii and G. Stacey for seeds and plasmids. This project was funded by a European Research Council Advanced Grant (ETAP-742985). M.F.K. and R.N. acknowledge the support of the EU MSCA-IF project CrysPINs (792329). M.K. was supported by the project POWR.03.05.00-00-Z302/17 Universitas Copernicana Thoruniensis in Futuro–IDS “Academia Copernicana”. CIDG acknowledges support from UKRI under Future Leaders Fellowship grant number MR/T020652/1.","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"publication":"Nature","ec_funded":1,"publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"isi":1,"project":[{"name":"Tracing Evolution of Auxin Transport and Polarity in Plants","_id":"261099A6-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"742985"}],"department":[{"_id":"JiFr"}],"title":"Adenylate cyclase activity of TIR1/AFB auxin receptors in plants","day":"03","date_updated":"2025-04-14T07:45:02Z","intvolume":"       611","oa_version":"Submitted Version","abstract":[{"lang":"eng","text":"The phytohormone auxin is the major coordinative signal in plant development1, mediating transcriptional reprogramming by a well-established canonical signalling pathway. TRANSPORT INHIBITOR RESPONSE 1 (TIR1)/AUXIN-SIGNALING F-BOX (AFB) auxin receptors are F-box subunits of ubiquitin ligase complexes. In response to auxin, they associate with Aux/IAA transcriptional repressors and target them for degradation via ubiquitination2,3. Here we identify adenylate cyclase (AC) activity as an additional function of TIR1/AFB receptors across land plants. Auxin, together with Aux/IAAs, stimulates cAMP production. Three separate mutations in the AC motif of the TIR1 C-terminal region, all of which abolish the AC activity, each render TIR1 ineffective in mediating gravitropism and sustained auxin-induced root growth inhibition, and also affect auxin-induced transcriptional regulation. These results highlight the importance of TIR1/AFB AC activity in canonical auxin signalling. They also identify a unique phytohormone receptor cassette combining F-box and AC motifs, and the role of cAMP as a second messenger in plants."}],"author":[{"orcid":"0000-0001-5187-8401","id":"44B04502-A9ED-11E9-B6FC-583AE6697425","first_name":"Linlin","full_name":"Qi, Linlin","last_name":"Qi"},{"full_name":"Kwiatkowski, Mateusz","last_name":"Kwiatkowski","first_name":"Mateusz"},{"id":"83c96512-15b2-11ec-abd3-b7eede36184f","first_name":"Huihuang","full_name":"Chen, Huihuang","last_name":"Chen"},{"full_name":"Hörmayer, Lukas","last_name":"Hörmayer","orcid":"0000-0001-8295-2926","first_name":"Lukas","id":"2EEE7A2A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Scott A","id":"2D99FE6A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4566-0593","last_name":"Sinclair","full_name":"Sinclair, Scott A"},{"last_name":"Zou","full_name":"Zou, Minxia","id":"5c243f41-03f3-11ec-841c-96faf48a7ef9","first_name":"Minxia"},{"first_name":"Charo I.","full_name":"del Genio, Charo I.","last_name":"del Genio"},{"first_name":"Martin F.","full_name":"Kubeš, Martin F.","last_name":"Kubeš"},{"full_name":"Napier, Richard","last_name":"Napier","first_name":"Richard"},{"first_name":"Krzysztof","last_name":"Jaworski","full_name":"Jaworski, Krzysztof"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","first_name":"Jiří","orcid":"0000-0002-8302-7596","last_name":"Friml","full_name":"Friml, Jiří"}],"article_type":"original","oa":1,"issue":"7934","publisher":"Springer Nature","doi":"10.1038/s41586-022-05369-7","language":[{"iso":"eng"}],"date_published":"2022-11-03T00:00:00Z","year":"2022","quality_controlled":"1","external_id":{"pmid":["36289340"],"isi":["000875061600013"]},"page":"133-138","_id":"12144","scopus_import":"1","month":"11","pmid":1,"citation":{"ieee":"L. Qi <i>et al.</i>, “Adenylate cyclase activity of TIR1/AFB auxin receptors in plants,” <i>Nature</i>, vol. 611, no. 7934. Springer Nature, pp. 133–138, 2022.","apa":"Qi, L., Kwiatkowski, M., Chen, H., Hörmayer, L., Sinclair, S. A., Zou, M., … Friml, J. (2022). Adenylate cyclase activity of TIR1/AFB auxin receptors in plants. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-022-05369-7\">https://doi.org/10.1038/s41586-022-05369-7</a>","ama":"Qi L, Kwiatkowski M, Chen H, et al. Adenylate cyclase activity of TIR1/AFB auxin receptors in plants. <i>Nature</i>. 2022;611(7934):133-138. doi:<a href=\"https://doi.org/10.1038/s41586-022-05369-7\">10.1038/s41586-022-05369-7</a>","chicago":"Qi, Linlin, Mateusz Kwiatkowski, Huihuang Chen, Lukas Hörmayer, Scott A Sinclair, Minxia Zou, Charo I. del Genio, et al. “Adenylate Cyclase Activity of TIR1/AFB Auxin Receptors in Plants.” <i>Nature</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41586-022-05369-7\">https://doi.org/10.1038/s41586-022-05369-7</a>.","ista":"Qi L, Kwiatkowski M, Chen H, Hörmayer L, Sinclair SA, Zou M, del Genio CI, Kubeš MF, Napier R, Jaworski K, Friml J. 2022. Adenylate cyclase activity of TIR1/AFB auxin receptors in plants. Nature. 611(7934), 133–138.","mla":"Qi, Linlin, et al. “Adenylate Cyclase Activity of TIR1/AFB Auxin Receptors in Plants.” <i>Nature</i>, vol. 611, no. 7934, Springer Nature, 2022, pp. 133–38, doi:<a href=\"https://doi.org/10.1038/s41586-022-05369-7\">10.1038/s41586-022-05369-7</a>.","short":"L. Qi, M. Kwiatkowski, H. Chen, L. Hörmayer, S.A. Sinclair, M. Zou, C.I. del Genio, M.F. Kubeš, R. Napier, K. Jaworski, J. Friml, Nature 611 (2022) 133–138."},"publication_status":"published","type":"journal_article","corr_author":"1","volume":611,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"intvolume":"        18","date_updated":"2025-04-14T07:46:59Z","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Embryo development requires biochemical signalling to generate patterns of cell fates and active mechanical forces to drive tissue shape changes. However, how these processes are coordinated, and how tissue patterning is preserved despite the cellular flows occurring during morphogenesis, remains poorly understood. Gastrulation is a crucial embryonic stage that involves both patterning and internalization of the mesendoderm germ layer tissue. Here we show that, in zebrafish embryos, a gradient in Nodal signalling orchestrates pattern-preserving internalization movements by triggering a motility-driven unjamming transition. In addition to its role as a morphogen determining embryo patterning, graded Nodal signalling mechanically subdivides the mesendoderm into a small fraction of highly protrusive leader cells, able to autonomously internalize via local unjamming, and less protrusive followers, which need to be pulled inwards by the leaders. The Nodal gradient further enforces a code of preferential adhesion coupling leaders to their immediate followers, resulting in a collective and ordered mode of internalization that preserves mesendoderm patterning. Integrating this dual mechanical role of Nodal signalling into minimal active particle simulations quantitatively predicts both physiological and experimentally perturbed internalization movements. This provides a quantitative framework for how a morphogen-encoded unjamming transition can bidirectionally couple tissue mechanics with patterning during complex three-dimensional morphogenesis."}],"license":"https://creativecommons.org/licenses/by/4.0/","author":[{"orcid":"0000-0003-4333-7503","id":"2E839F16-F248-11E8-B48F-1D18A9856A87","first_name":"Diana C","full_name":"Nunes Pinheiro, Diana C","last_name":"Nunes Pinheiro"},{"first_name":"Roland","id":"4039350E-F248-11E8-B48F-1D18A9856A87","last_name":"Kardos","full_name":"Kardos, Roland"},{"orcid":"0000-0001-6005-1561","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B","last_name":"Hannezo"},{"first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J"}],"isi":1,"has_accepted_license":"1","project":[{"grant_number":"ALTF 850-2017","_id":"26520D1E-B435-11E9-9278-68D0E5697425","name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation"},{"_id":"26520D1E-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 850-2017","name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation"},{"name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020","grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E"},{"grant_number":"742573","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation"}],"department":[{"_id":"CaHe"},{"_id":"EdHa"}],"title":"Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming","day":"01","ddc":["570"],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"publication":"Nature Physics","ec_funded":1,"publication_identifier":{"issn":["1745-2473"],"eissn":["1745-2481"]},"article_processing_charge":"No","file_date_updated":"2023-01-27T07:32:01Z","status":"public","date_created":"2023-01-16T09:45:19Z","acknowledgement":"We thank K. Sampath, A. Pauli and Y. Bellaїche for feedback on the manuscript. We also thank the members of the Heisenberg group, in particular A. Schauer and F. Nur Arslan, for help, technical advice and discussions, and the Bioimaging and Life Science facilities at IST\r\nAustria for continuous support. We thank C. Flandoli for the artwork in the figures. This work was supported by postdoctoral fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P. and the European Union (European Research Council starting grant 851288 to É.H. and European Research Council advanced grant 742573 to C.-P.H.).","citation":{"ama":"Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. <i>Nature Physics</i>. 2022;18(12):1482-1493. doi:<a href=\"https://doi.org/10.1038/s41567-022-01787-6\">10.1038/s41567-022-01787-6</a>","apa":"Nunes Pinheiro, D. C., Kardos, R., Hannezo, E. B., &#38; Heisenberg, C.-P. J. (2022). Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-022-01787-6\">https://doi.org/10.1038/s41567-022-01787-6</a>","ieee":"D. C. Nunes Pinheiro, R. Kardos, E. B. Hannezo, and C.-P. J. Heisenberg, “Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming,” <i>Nature Physics</i>, vol. 18, no. 12. Springer Nature, pp. 1482–1493, 2022.","short":"D.C. Nunes Pinheiro, R. Kardos, E.B. Hannezo, C.-P.J. Heisenberg, Nature Physics 18 (2022) 1482–1493.","mla":"Nunes Pinheiro, Diana C., et al. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis via Motility-Driven Unjamming.” <i>Nature Physics</i>, vol. 18, no. 12, Springer Nature, 2022, pp. 1482–93, doi:<a href=\"https://doi.org/10.1038/s41567-022-01787-6\">10.1038/s41567-022-01787-6</a>.","chicago":"Nunes Pinheiro, Diana C, Roland Kardos, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis via Motility-Driven Unjamming.” <i>Nature Physics</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41567-022-01787-6\">https://doi.org/10.1038/s41567-022-01787-6</a>.","ista":"Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. 2022. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nature Physics. 18(12), 1482–1493."},"publication_status":"published","volume":18,"type":"journal_article","corr_author":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"_id":"12209","scopus_import":"1","month":"12","year":"2022","quality_controlled":"1","external_id":{"isi":["000871319900002"]},"page":"1482-1493","article_type":"original","keyword":["General Physics and Astronomy"],"oa":1,"file":[{"success":1,"creator":"dernst","relation":"main_file","date_created":"2023-01-27T07:32:01Z","file_size":36703569,"date_updated":"2023-01-27T07:32:01Z","content_type":"application/pdf","access_level":"open_access","checksum":"c86a8e8d80d1bfc46d56a01e88a2526a","file_name":"2022_NaturePhysics_Pinheiro.pdf","file_id":"12412"}],"issue":"12","doi":"10.1038/s41567-022-01787-6","language":[{"iso":"eng"}],"publisher":"Springer Nature","date_published":"2022-12-01T00:00:00Z"},{"external_id":{"isi":["000882769800009"],"pmid":["36081349"]},"page":"1533-1542","quality_controlled":"1","year":"2022","file":[{"file_size":2307251,"content_type":"application/pdf","date_updated":"2023-01-30T07:46:51Z","file_name":"2022_MolecularPlant_Johnson.pdf","access_level":"open_access","checksum":"04d5c12490052d03e4dc4412338a43dd","file_id":"12435","success":1,"creator":"dernst","relation":"main_file","date_created":"2023-01-30T07:46:51Z"}],"oa":1,"language":[{"iso":"eng"}],"publisher":"Elsevier","date_published":"2022-10-03T00:00:00Z","doi":"10.1016/j.molp.2022.09.003","issue":"10","article_type":"original","keyword":["Plant Science","Molecular Biology"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication_status":"published","citation":{"short":"A.J. Johnson, W. Kaufmann, C.M. Sommer, T. Costanzo, D.A. Dahhan, S.Y. Bednarek, J. Friml, Molecular Plant 15 (2022) 1533–1542.","chicago":"Johnson, Alexander J, Walter Kaufmann, Christoph M Sommer, Tommaso Costanzo, Dana A. Dahhan, Sebastian Y. Bednarek, and Jiří Friml. “Three-Dimensional Visualization of Planta Clathrin-Coated Vesicles at Ultrastructural Resolution.” <i>Molecular Plant</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">https://doi.org/10.1016/j.molp.2022.09.003</a>.","ista":"Johnson AJ, Kaufmann W, Sommer CM, Costanzo T, Dahhan DA, Bednarek SY, Friml J. 2022. Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. Molecular Plant. 15(10), 1533–1542.","mla":"Johnson, Alexander J., et al. “Three-Dimensional Visualization of Planta Clathrin-Coated Vesicles at Ultrastructural Resolution.” <i>Molecular Plant</i>, vol. 15, no. 10, Elsevier, 2022, pp. 1533–42, doi:<a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">10.1016/j.molp.2022.09.003</a>.","ieee":"A. J. Johnson <i>et al.</i>, “Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution,” <i>Molecular Plant</i>, vol. 15, no. 10. Elsevier, pp. 1533–1542, 2022.","ama":"Johnson AJ, Kaufmann W, Sommer CM, et al. Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. <i>Molecular Plant</i>. 2022;15(10):1533-1542. doi:<a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">10.1016/j.molp.2022.09.003</a>","apa":"Johnson, A. J., Kaufmann, W., Sommer, C. M., Costanzo, T., Dahhan, D. A., Bednarek, S. Y., &#38; Friml, J. (2022). Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. <i>Molecular Plant</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">https://doi.org/10.1016/j.molp.2022.09.003</a>"},"type":"journal_article","corr_author":"1","volume":15,"pmid":1,"month":"10","scopus_import":"1","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"_id":"12239","publication_identifier":{"issn":["1674-2052"]},"publication":"Molecular Plant","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"Bio"}],"date_created":"2023-01-16T09:51:49Z","file_date_updated":"2023-01-30T07:46:51Z","status":"public","acknowledgement":"A.J. is supported by funding from the Austrian Science Fund I3630B25 (to J.F.). This research was supported by the Scientific Service Units of Institute of Science and Technology Austria (ISTA) through resources provided by the Electron Microscopy Facility, Lab Support Facility, and the Imaging and Optics Facility. We acknowledge Prof. David Robinson (Heidelberg) and Prof. Jan Traas (Lyon) for making us aware of previously published classical on-grid preparation methods. No conflict of interest declared.","article_processing_charge":"Yes (via OA deal)","author":[{"full_name":"Johnson, Alexander J","last_name":"Johnson","orcid":"0000-0002-2739-8843","first_name":"Alexander J","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","full_name":"Kaufmann, Walter","last_name":"Kaufmann"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"last_name":"Costanzo","full_name":"Costanzo, Tommaso","id":"D93824F4-D9BA-11E9-BB12-F207E6697425","first_name":"Tommaso","orcid":"0000-0001-9732-3815"},{"full_name":"Dahhan, Dana A.","last_name":"Dahhan","first_name":"Dana A."},{"last_name":"Bednarek","full_name":"Bednarek, Sebastian Y.","first_name":"Sebastian Y."},{"first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","last_name":"Friml","full_name":"Friml, Jiří"}],"oa_version":"Published Version","date_updated":"2025-04-15T07:32:09Z","intvolume":"        15","abstract":[{"lang":"eng","text":"Biological systems are the sum of their dynamic three-dimensional (3D) parts. Therefore, it is critical to study biological structures in 3D and at high resolution to gain insights into their physiological functions. Electron microscopy of metal replicas of unroofed cells and isolated organelles has been a key technique to visualize intracellular structures at nanometer resolution. However, many of these methods require specialized equipment and personnel to complete them. Here, we present novel accessible methods to analyze biological structures in unroofed cells and biochemically isolated organelles in 3D and at nanometer resolution, focusing on Arabidopsis clathrin-coated vesicles (CCVs). While CCVs are essential trafficking organelles, their detailed structural information is lacking due to their poor preservation when observed via classical electron microscopy protocols experiments. First, we establish a method to visualize CCVs in unroofed cells using scanning transmission electron microscopy tomography, providing sufficient resolution to define the clathrin coat arrangements. Critically, the samples are prepared directly on electron microscopy grids, removing the requirement to use extremely corrosive acids, thereby enabling the use of this method in any electron microscopy lab. Secondly, we demonstrate that this standardized sample preparation allows the direct comparison of isolated CCV samples with those visualized in cells. Finally, to facilitate the high-throughput and robust screening of metal replicated samples, we provide a deep learning analysis method to screen the “pseudo 3D” morphologies of CCVs imaged with 2D modalities. Collectively, our work establishes accessible ways to examine the 3D structure of biological samples and provide novel insights into the structure of plant CCVs."}],"title":"Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution","ddc":["580"],"day":"03","isi":1,"has_accepted_license":"1","department":[{"_id":"JiFr"},{"_id":"EM-Fac"},{"_id":"Bio"}],"project":[{"name":"Molecular mechanisms of endocytic cargo recognition in plants","_id":"26538374-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03630"}]},{"title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","ddc":["570"],"day":"15","has_accepted_license":"1","isi":1,"department":[{"_id":"MaJö"},{"_id":"PeJo"}],"project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"name":"Circuits of Visual Attention","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","grant_number":"756502","call_identifier":"H2020"},{"name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312"},{"grant_number":"LT000256","_id":"266D407A-B435-11E9-9278-68D0E5697425","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus"},{"grant_number":"ALTF 1098-2017","_id":"264FEA02-B435-11E9-9278-68D0E5697425","name":"Connecting sensory with motor processing in the superior colliculus"}],"author":[{"full_name":"Sumser, Anton L","last_name":"Sumser","orcid":"0000-0002-4792-1881","id":"3320A096-F248-11E8-B48F-1D18A9856A87","first_name":"Anton L"},{"id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","first_name":"Maximilian A","orcid":"0000-0002-3937-1330","last_name":"Jösch","full_name":"Jösch, Maximilian A"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav","full_name":"Ben Simon, Yoav","last_name":"Ben Simon"}],"oa_version":"Published Version","article_number":"79848","date_updated":"2025-04-15T08:29:05Z","intvolume":"        11","abstract":[{"text":"To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo.","lang":"eng"}],"date_created":"2023-01-16T10:04:15Z","file_date_updated":"2023-01-30T11:50:53Z","status":"public","acknowledgement":"We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).","article_processing_charge":"No","ec_funded":1,"publication_identifier":{"eissn":["2050-084X"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"publication":"eLife","pmid":1,"scopus_import":"1","month":"09","_id":"12288","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication_status":"published","citation":{"ama":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>","apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., &#38; Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>","ieee":"A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>, vol. 11, 79848, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>.","ista":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848.","chicago":"Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>."},"volume":11,"corr_author":"1","type":"journal_article","file":[{"success":1,"relation":"main_file","creator":"dernst","date_created":"2023-01-30T11:50:53Z","file_size":8506811,"date_updated":"2023-01-30T11:50:53Z","content_type":"application/pdf","access_level":"open_access","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","file_name":"2022_eLife_Sumser.pdf","file_id":"12463"}],"oa":1,"language":[{"iso":"eng"}],"date_published":"2022-09-15T00:00:00Z","doi":"10.7554/elife.79848","publisher":"eLife Sciences Publications","article_type":"original","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"external_id":{"isi":["000892204300001"],"pmid":["36040301"]},"quality_controlled":"1","year":"2022"},{"publication_status":"published","citation":{"ama":"Friml J, Gallei MC, Gelová Z, et al. ABP1–TMK auxin perception for global phosphorylation and auxin canalization. <i>Nature</i>. 2022;609(7927):575-581. doi:<a href=\"https://doi.org/10.1038/s41586-022-05187-x\">10.1038/s41586-022-05187-x</a>","apa":"Friml, J., Gallei, M. C., Gelová, Z., Johnson, A. J., Mazur, E., Monzer, A., … Rakusová, H. (2022). ABP1–TMK auxin perception for global phosphorylation and auxin canalization. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-022-05187-x\">https://doi.org/10.1038/s41586-022-05187-x</a>","ieee":"J. Friml <i>et al.</i>, “ABP1–TMK auxin perception for global phosphorylation and auxin canalization,” <i>Nature</i>, vol. 609, no. 7927. Springer Nature, pp. 575–581, 2022.","short":"J. Friml, M.C. Gallei, Z. Gelová, A.J. Johnson, E. Mazur, A. Monzer, L. Rodriguez Solovey, M. Roosjen, I. Verstraeten, B.D. Živanović, M. Zou, L. Fiedler, C. Giannini, P. Grones, M. Hrtyan, W. Kaufmann, A. Kuhn, M. Narasimhan, M. Randuch, N. Rýdza, K. Takahashi, S. Tan, A. Teplova, T. Kinoshita, D. Weijers, H. Rakusová, Nature 609 (2022) 575–581.","chicago":"Friml, Jiří, Michelle C Gallei, Zuzana Gelová, Alexander J Johnson, Ewa Mazur, Aline Monzer, Lesia Rodriguez Solovey, et al. “ABP1–TMK Auxin Perception for Global Phosphorylation and Auxin Canalization.” <i>Nature</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41586-022-05187-x\">https://doi.org/10.1038/s41586-022-05187-x</a>.","mla":"Friml, Jiří, et al. “ABP1–TMK Auxin Perception for Global Phosphorylation and Auxin Canalization.” <i>Nature</i>, vol. 609, no. 7927, Springer Nature, 2022, pp. 575–81, doi:<a href=\"https://doi.org/10.1038/s41586-022-05187-x\">10.1038/s41586-022-05187-x</a>.","ista":"Friml J, Gallei MC, Gelová Z, Johnson AJ, Mazur E, Monzer A, Rodriguez Solovey L, Roosjen M, Verstraeten I, Živanović BD, Zou M, Fiedler L, Giannini C, Grones P, Hrtyan M, Kaufmann W, Kuhn A, Narasimhan M, Randuch M, Rýdza N, Takahashi K, Tan S, Teplova A, Kinoshita T, Weijers D, Rakusová H. 2022. ABP1–TMK auxin perception for global phosphorylation and auxin canalization. Nature. 609(7927), 575–581."},"volume":609,"corr_author":"1","type":"journal_article","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"12291","pmid":1,"scopus_import":"1","month":"09","quality_controlled":"1","year":"2022","external_id":{"pmid":["36071161"],"isi":["000851357500002"]},"page":"575-581","article_type":"original","file":[{"file_id":"14483","access_level":"open_access","checksum":"a6055c606aefb900bf62ae3e7d15f921","file_name":"Friml Nature 2022_merged.pdf","date_updated":"2023-11-02T17:12:37Z","content_type":"application/pdf","file_size":79774945,"date_created":"2023-11-02T17:12:37Z","relation":"main_file","creator":"amally","success":1}],"oa":1,"doi":"10.1038/s41586-022-05187-x","publisher":"Springer Nature","language":[{"iso":"eng"}],"date_published":"2022-09-15T00:00:00Z","issue":"7927","oa_version":"Submitted Version","date_updated":"2026-04-07T11:52:15Z","intvolume":"       609","abstract":[{"lang":"eng","text":"The phytohormone auxin triggers transcriptional reprogramming through a well-characterized perception machinery in the nucleus. By contrast, mechanisms that underlie fast effects of auxin, such as the regulation of ion fluxes, rapid phosphorylation of proteins or auxin feedback on its transport, remain unclear1,2,3. Whether auxin-binding protein 1 (ABP1) is an auxin receptor has been a source of debate for decades1,4. Here we show that a fraction of Arabidopsis thaliana ABP1 is secreted and binds auxin specifically at an acidic pH that is typical of the apoplast. ABP1 and its plasma-membrane-localized partner, transmembrane kinase 1 (TMK1), are required for the auxin-induced ultrafast global phospho-response and for downstream processes that include the activation of H+-ATPase and accelerated cytoplasmic streaming. abp1 and tmk mutants cannot establish auxin-transporting channels and show defective auxin-induced vasculature formation and regeneration. An ABP1(M2X) variant that lacks the capacity to bind auxin is unable to complement these defects in abp1 mutants. These data indicate that ABP1 is the auxin receptor for TMK1-based cell-surface signalling, which mediates the global phospho-response and auxin canalization."}],"author":[{"full_name":"Friml, Jiří","last_name":"Friml","orcid":"0000-0002-8302-7596","first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1286-7368","id":"35A03822-F248-11E8-B48F-1D18A9856A87","first_name":"Michelle C","full_name":"Gallei, Michelle C","last_name":"Gallei"},{"id":"0AE74790-0E0B-11E9-ABC7-1ACFE5697425","first_name":"Zuzana","orcid":"0000-0003-4783-1752","last_name":"Gelová","full_name":"Gelová, Zuzana"},{"id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander J","orcid":"0000-0002-2739-8843","last_name":"Johnson","full_name":"Johnson, Alexander J"},{"full_name":"Mazur, Ewa","last_name":"Mazur","first_name":"Ewa"},{"last_name":"Monzer","full_name":"Monzer, Aline","first_name":"Aline","id":"2DB5D88C-D7B3-11E9-B8FD-7907E6697425"},{"orcid":"0000-0002-7244-7237","id":"3922B506-F248-11E8-B48F-1D18A9856A87","first_name":"Lesia","full_name":"Rodriguez Solovey, Lesia","last_name":"Rodriguez Solovey"},{"last_name":"Roosjen","full_name":"Roosjen, Mark","first_name":"Mark"},{"last_name":"Verstraeten","full_name":"Verstraeten, Inge","first_name":"Inge","id":"362BF7FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7241-2328"},{"first_name":"Branka D.","last_name":"Živanović","full_name":"Živanović, Branka D."},{"id":"5c243f41-03f3-11ec-841c-96faf48a7ef9","first_name":"Minxia","full_name":"Zou, Minxia","last_name":"Zou"},{"full_name":"Fiedler, Lukas","last_name":"Fiedler","id":"7c417475-8972-11ed-ae7b-8b674ca26986","first_name":"Lukas"},{"last_name":"Giannini","full_name":"Giannini, Caterina","id":"e3fdddd5-f6e0-11ea-865d-ca99ee6367f4","first_name":"Caterina"},{"first_name":"Peter","full_name":"Grones, Peter","last_name":"Grones"},{"id":"45A71A74-F248-11E8-B48F-1D18A9856A87","first_name":"Mónika","full_name":"Hrtyan, Mónika","last_name":"Hrtyan"},{"orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","full_name":"Kaufmann, Walter","last_name":"Kaufmann"},{"full_name":"Kuhn, Andre","last_name":"Kuhn","first_name":"Andre"},{"orcid":"0000-0002-8600-0671","id":"44BF24D0-F248-11E8-B48F-1D18A9856A87","first_name":"Madhumitha","full_name":"Narasimhan, Madhumitha","last_name":"Narasimhan"},{"first_name":"Marek","id":"6ac4636d-15b2-11ec-abd3-fb8df79972ae","last_name":"Randuch","full_name":"Randuch, Marek"},{"last_name":"Rýdza","full_name":"Rýdza, Nikola","first_name":"Nikola"},{"full_name":"Takahashi, Koji","last_name":"Takahashi","first_name":"Koji"},{"orcid":"0000-0002-0471-8285","id":"2DE75584-F248-11E8-B48F-1D18A9856A87","first_name":"Shutang","full_name":"Tan, Shutang","last_name":"Tan"},{"last_name":"Teplova","full_name":"Teplova, Anastasiia","first_name":"Anastasiia","id":"e3736151-106c-11ec-b916-c2558e2762c6"},{"first_name":"Toshinori","last_name":"Kinoshita","full_name":"Kinoshita, Toshinori"},{"first_name":"Dolf","last_name":"Weijers","full_name":"Weijers, Dolf"},{"first_name":"Hana","full_name":"Rakusová, Hana","last_name":"Rakusová"}],"has_accepted_license":"1","isi":1,"department":[{"_id":"JiFr"},{"_id":"GradSch"},{"_id":"EvBe"},{"_id":"EM-Fac"}],"project":[{"name":"Tracing Evolution of Auxin Transport and Polarity in Plants","call_identifier":"H2020","grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425"},{"name":"RNA-directed DNA methylation in plant development","call_identifier":"FWF","grant_number":"P29988","_id":"262EF96E-B435-11E9-9278-68D0E5697425"}],"title":"ABP1–TMK auxin perception for global phosphorylation and auxin canalization","ddc":["580"],"day":"15","related_material":{"record":[{"status":"public","id":"19395","relation":"dissertation_contains"},{"status":"public","relation":"dissertation_contains","id":"20364"}]},"publication":"Nature","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"LifeSc"}],"ec_funded":1,"publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"article_processing_charge":"No","date_created":"2023-01-16T10:04:48Z","file_date_updated":"2023-11-02T17:12:37Z","status":"public","acknowledgement":"We acknowledge K. Kubiasová for excellent technical assistance, J. Neuhold, A. Lehner and A. Sedivy for technical assistance with protein production and purification at Vienna Biocenter Core Facilities; Creoptix for performing GCI; and the Bioimaging, Electron Microscopy and Life Science Facilities at ISTA, the Plant Sciences Core Facility of CEITEC Masaryk University, the Core Facility CELLIM (MEYS CR, LM2018129 Czech-BioImaging) and J. Sprakel for their assistance. J.F. is grateful to R. Napier for many insightful suggestions and support. We thank all past and present members of the Friml group for their support and for other contributions to this effort to clarify the controversial role of ABP1 over the past seven years. The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 742985 to J.F. and 833867 to D.W.); the Austrian Science Fund (FWF; P29988 to J.F.); the Netherlands Organization for Scientific Research (NWO; VICI grant 865.14.001 to D.W. and VENI grant VI.Veni.212.003 to A.K.); the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract no. 451-03-68/2022-14/200053 to B.D.Ž.); and the MEXT/JSPS KAKENHI to K.T. (20K06685) and T.K. (20H05687 and 20H05910)."},{"month":"09","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"_id":"12368","OA_place":"publisher","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publication_status":"published","supervisor":[{"last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566"}],"citation":{"apa":"Arslan, F. N. (2022). <i>Remodeling of E-cadherin-mediated contacts via cortical  flows</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12153\">https://doi.org/10.15479/at:ista:12153</a>","ama":"Arslan FN. Remodeling of E-cadherin-mediated contacts via cortical  flows. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:12153\">10.15479/at:ista:12153</a>","ieee":"F. N. Arslan, “Remodeling of E-cadherin-mediated contacts via cortical  flows,” Institute of Science and Technology Austria, 2022.","short":"F.N. Arslan, Remodeling of E-Cadherin-Mediated Contacts via Cortical  Flows, Institute of Science and Technology Austria, 2022.","ista":"Arslan FN. 2022. Remodeling of E-cadherin-mediated contacts via cortical  flows. Institute of Science and Technology Austria.","mla":"Arslan, Feyza N. <i>Remodeling of E-Cadherin-Mediated Contacts via Cortical  Flows</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:12153\">10.15479/at:ista:12153</a>.","chicago":"Arslan, Feyza N. “Remodeling of E-Cadherin-Mediated Contacts via Cortical  Flows.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:12153\">https://doi.org/10.15479/at:ista:12153</a>."},"degree_awarded":"PhD","corr_author":"1","type":"dissertation","file":[{"success":1,"relation":"main_file","creator":"cchlebak","date_created":"2023-01-25T10:52:46Z","file_size":14581024,"date_updated":"2023-01-25T10:52:46Z","content_type":"application/pdf","checksum":"e54a3e69b83ebf166544164afd25608e","access_level":"open_access","file_name":"THESIS_FINAL_FArslan_pdfa.pdf","file_id":"12369"}],"oa":1,"date_published":"2022-09-29T00:00:00Z","publisher":"Institute of Science and Technology Austria","doi":"10.15479/at:ista:12153","language":[{"iso":"eng"}],"page":"113","year":"2022","title":"Remodeling of E-cadherin-mediated contacts via cortical  flows","ddc":["570"],"day":"29","alternative_title":["ISTA Thesis"],"has_accepted_license":"1","department":[{"_id":"GradSch"},{"_id":"CaHe"}],"project":[{"_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573","call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation"}],"author":[{"full_name":"Arslan, Feyza N","last_name":"Arslan","orcid":"0000-0001-5809-9566","id":"49DA7910-F248-11E8-B48F-1D18A9856A87","first_name":"Feyza N"}],"oa_version":"Published Version","date_updated":"2026-06-18T19:47:50Z","abstract":[{"text":"Metazoan development relies on the formation and remodeling of cell-cell contacts. The \r\nbinding of adhesion receptors and remodeling of the actomyosin cell cortex at cell-cell \r\ninteraction sites have been implicated in cell-cell contact formation. Yet, how these two \r\nprocesses functionally interact to drive cell-cell contact expansion and strengthening \r\nremains unclear. Here, we study how primary germ layer progenitor cells from zebrafish \r\nbind to supported lipid bilayers (SLB) functionalized with E-cadherin ectodomains as an \r\nassay system for monitoring cell-cell contact formation at high spatiotemporal resolution. \r\nWe show that cell-cell contact formation represents a two-tiered process: E-cadherin\u0002mediated downregulation of the small GTPase RhoA at the forming contact leads to both \r\ndepletion of Myosin-2 and decrease of F-actin. This is followed by centrifugal actin \r\nnetwork flows at the contact triggered by a sharp gradient of Myosin-2 at the rim of the \r\ncontact zone, with Myosin-2 displaying higher cortical localization outside than inside of \r\nthe contact. These centrifugal cortical actin flows, in turn, not only further dilute the actin \r\nnetwork at the contact disc, but also lead to an accumulation of both F-actin and E\u0002cadherin at the contact rim. Eventually, this combination of actomyosin downregulation \r\nand flows at the contact contribute to the characteristic molecular organization implicated \r\nin contact formation and maintenance: depletion of cortical actomyosin at the contact disc, \r\ndriving contact expansion by lowering interfacial tension at the contact, and accumulation \r\nof both E-cadherin and F-actin at the contact rim, mechanically linking the contractile \r\ncortices of the adhering cells. Thus, using a biomimetic assay, we exemplify how \r\nadhesion signaling and cell mechanics function together to modulate the spatial \r\norganization of cell-cell contacts.","lang":"eng"}],"date_created":"2023-01-25T10:43:24Z","file_date_updated":"2023-01-25T10:52:46Z","status":"public","article_processing_charge":"No","ec_funded":1,"publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-025-1 "]},"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"NanoFab"}],"related_material":{"record":[{"relation":"part_of_dissertation","id":"9350","status":"public"}]}},{"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"_id":"10712","pmid":1,"month":"02","scopus_import":"1","publication_status":"published","citation":{"ama":"Roblek M, Bicher J, van Gogh M, et al. The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. <i>Frontiers in Oncology</i>. 2022;12. doi:<a href=\"https://doi.org/10.3389/fonc.2022.777634\">10.3389/fonc.2022.777634</a>","apa":"Roblek, M., Bicher, J., van Gogh, M., György, A., Seeböck, R., Szulc, B., … Siekhaus, D. E. (2022). The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. <i>Frontiers in Oncology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fonc.2022.777634\">https://doi.org/10.3389/fonc.2022.777634</a>","ieee":"M. Roblek <i>et al.</i>, “The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis,” <i>Frontiers in Oncology</i>, vol. 12. Frontiers, 2022.","mla":"Roblek, Marko, et al. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor Metastasis.” <i>Frontiers in Oncology</i>, vol. 12, 777634, Frontiers, 2022, doi:<a href=\"https://doi.org/10.3389/fonc.2022.777634\">10.3389/fonc.2022.777634</a>.","ista":"Roblek M, Bicher J, van Gogh M, György A, Seeböck R, Szulc B, Damme M, Olczak M, Borsig L, Siekhaus DE. 2022. The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. Frontiers in Oncology. 12, 777634.","chicago":"Roblek, Marko, Julia Bicher, Merel van Gogh, Attila György, Rita Seeböck, Bozena Szulc, Markus Damme, Mariusz Olczak, Lubor Borsig, and Daria E Siekhaus. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor Metastasis.” <i>Frontiers in Oncology</i>. Frontiers, 2022. <a href=\"https://doi.org/10.3389/fonc.2022.777634\">https://doi.org/10.3389/fonc.2022.777634</a>.","short":"M. Roblek, J. Bicher, M. van Gogh, A. György, R. Seeböck, B. Szulc, M. Damme, M. Olczak, L. Borsig, D.E. Siekhaus, Frontiers in Oncology 12 (2022)."},"corr_author":"1","volume":12,"type":"journal_article","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_type":"original","file":[{"date_updated":"2022-02-08T13:26:40Z","content_type":"application/pdf","file_size":6303227,"file_id":"10751","access_level":"open_access","checksum":"63dfecf30c5bbf9408b3512bd603f78c","file_name":"2022_FrontiersOncol_Roblek.pdf","creator":"cchlebak","relation":"main_file","success":1,"date_created":"2022-02-08T13:26:40Z"}],"oa":1,"doi":"10.3389/fonc.2022.777634","publisher":"Frontiers","date_published":"2022-02-08T00:00:00Z","language":[{"iso":"eng"}],"quality_controlled":"1","year":"2022","external_id":{"isi":["000760618800001"],"pmid":["35211397"]},"has_accepted_license":"1","isi":1,"department":[{"_id":"DaSi"}],"project":[{"grant_number":"LSC16-021","_id":"2637E9C0-B435-11E9-9278-68D0E5697425","name":"Investigating the role of the novel major superfamily facilitator transporter family member MFSD1 in metastasis"}],"title":"The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis","ddc":["570"],"day":"08","article_number":"777634","oa_version":"Published Version","intvolume":"        12","date_updated":"2025-06-11T13:56:08Z","abstract":[{"lang":"eng","text":"Solute carriers are increasingly recognized as participating in a plethora of pathologies, including cancer. We describe here the involvement of the orphan solute carrier MFSD1 in the regulation of tumor cell migration. Loss of MFSD1 enabled higher levels of metastasis in a mouse model. We identified an increased migratory potential in MFSD1-/- tumor cells which was mediated by increased focal adhesion turn-over, reduced stability of mature inactive β1 integrin, and the resulting increased integrin activation index. We show that MFSD1 promoted recycling to the cell surface of endocytosed inactive β1 integrin and thereby protected β1 integrin from proteolytic degradation; this led to dampening of the integrin activation index. Furthermore, down-regulation of MFSD1 expression was observed during early steps of tumorigenesis and higher MFSD1 expression levels correlate with a better cancer patient prognosis. In sum, we describe a requirement for endolysosomal MFSD1 in efficient β1 integrin recycling to suppress tumor spread."}],"author":[{"first_name":"Marko","id":"3047D808-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9588-1389","last_name":"Roblek","full_name":"Roblek, Marko"},{"id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Bicher","full_name":"Bicher, Julia"},{"full_name":"van Gogh, Merel","last_name":"van Gogh","first_name":"Merel"},{"last_name":"György","full_name":"György, Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","first_name":"Attila","orcid":"0000-0002-1819-198X"},{"full_name":"Seeböck, Rita","last_name":"Seeböck","first_name":"Rita"},{"first_name":"Bozena","last_name":"Szulc","full_name":"Szulc, Bozena"},{"full_name":"Damme, Markus","last_name":"Damme","first_name":"Markus"},{"first_name":"Mariusz","last_name":"Olczak","full_name":"Olczak, Mariusz"},{"last_name":"Borsig","full_name":"Borsig, Lubor","first_name":"Lubor"},{"full_name":"Siekhaus, Daria E","last_name":"Siekhaus","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E"}],"article_processing_charge":"Yes (via OA deal)","date_created":"2022-02-01T10:33:50Z","status":"public","file_date_updated":"2022-02-08T13:26:40Z","acknowledgement":"We thank M. Sixt, A. Leithner, and J. Alanko for helpful advice and the BioImaging Facility at IST Austria for technical support and assistance. We thank the Siekhaus Lab for the careful review of the manuscript and their input. MR and DS were funded by the NO Forschungs- und Bildungsges.m.b.H. (LS16-021) and IST core funding. MD was funded by Deutsche Forschungsgemeinschaft (DA 1785-1).","acknowledged_ssus":[{"_id":"Bio"}],"related_material":{"link":[{"description":"News on IST Homepage","relation":"confirmation","url":"https://ist.ac.at/en/news/suppressing-the-spread-of-tumors/"}]},"publication":"Frontiers in Oncology","publication_identifier":{"issn":["2234-943X"]}},{"type":"journal_article","corr_author":"1","volume":376,"citation":{"short":"M. Akhmanova, S. Emtenani, D. Krueger, A. György, M. Pereira Guarda, M. Vlasov, F. Vlasov, A. Akopian, A. Ratheesh, S. De Renzis, D.E. Siekhaus, Science 376 (2022) 394–396.","mla":"Akhmanova, Maria, et al. “Cell Division in Tissues Enables Macrophage Infiltration.” <i>Science</i>, vol. 376, no. 6591, American Association for the Advancement of Science, 2022, pp. 394–96, doi:<a href=\"https://doi.org/10.1126/science.abj0425\">10.1126/science.abj0425</a>.","ista":"Akhmanova M, Emtenani S, Krueger D, György A, Pereira Guarda M, Vlasov M, Vlasov F, Akopian A, Ratheesh A, De Renzis S, Siekhaus DE. 2022. Cell division in tissues enables macrophage infiltration. Science. 376(6591), 394–396.","chicago":"Akhmanova, Maria, Shamsi Emtenani, Daniel Krueger, Attila György, Mariana Pereira Guarda, Mikhail Vlasov, Fedor Vlasov, et al. “Cell Division in Tissues Enables Macrophage Infiltration.” <i>Science</i>. American Association for the Advancement of Science, 2022. <a href=\"https://doi.org/10.1126/science.abj0425\">https://doi.org/10.1126/science.abj0425</a>.","ieee":"M. Akhmanova <i>et al.</i>, “Cell division in tissues enables macrophage infiltration,” <i>Science</i>, vol. 376, no. 6591. American Association for the Advancement of Science, pp. 394–396, 2022.","ama":"Akhmanova M, Emtenani S, Krueger D, et al. Cell division in tissues enables macrophage infiltration. <i>Science</i>. 2022;376(6591):394-396. doi:<a href=\"https://doi.org/10.1126/science.abj0425\">10.1126/science.abj0425</a>","apa":"Akhmanova, M., Emtenani, S., Krueger, D., György, A., Pereira Guarda, M., Vlasov, M., … Siekhaus, D. E. (2022). Cell division in tissues enables macrophage infiltration. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.abj0425\">https://doi.org/10.1126/science.abj0425</a>"},"publication_status":"published","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10713","tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"scopus_import":"1","month":"04","pmid":1,"year":"2022","quality_controlled":"1","page":"394-396","external_id":{"isi":["000788553700039"],"pmid":["35446632"]},"article_type":"original","issue":"6591","date_published":"2022-04-22T00:00:00Z","publisher":"American Association for the Advancement of Science","doi":"10.1126/science.abj0425","language":[{"iso":"eng"}],"oa":1,"abstract":[{"text":"Cells migrate through crowded microenvironments within tissues during normal development, immune response, and cancer metastasis. Although migration through pores and tracks in the extracellular matrix (ECM) has been well studied, little is known about cellular traversal into confining cell-dense tissues. We find that embryonic tissue invasion by Drosophila macrophages requires division of an epithelial ectodermal cell at the site of entry. Dividing ectodermal cells disassemble ECM attachment formed by integrin-mediated focal adhesions next to mesodermal cells, allowing macrophages to move their nuclei ahead and invade between two immediately adjacent tissues. Invasion efficiency depends on division frequency, but reduction of adhesion strength allows macrophage entry independently of division. This work demonstrates that tissue dynamics can regulate cellular infiltration.","lang":"eng"}],"intvolume":"       376","date_updated":"2025-04-15T07:25:41Z","oa_version":"Preprint","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","author":[{"full_name":"Akhmanova, Maria","last_name":"Akhmanova","orcid":"0000-0003-1522-3162","id":"3425EC26-F248-11E8-B48F-1D18A9856A87","first_name":"Maria"},{"last_name":"Emtenani","full_name":"Emtenani, Shamsi","id":"49D32318-F248-11E8-B48F-1D18A9856A87","first_name":"Shamsi","orcid":"0000-0001-6981-6938"},{"first_name":"Daniel","last_name":"Krueger","full_name":"Krueger, Daniel"},{"first_name":"Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X","last_name":"György","full_name":"György, Attila"},{"orcid":"0000-0001-8238-480X","id":"6de81d9d-e2f2-11eb-945a-af8bc2a60b26","first_name":"Mariana","full_name":"Pereira Guarda, Mariana","last_name":"Pereira Guarda"},{"last_name":"Vlasov","full_name":"Vlasov, Mikhail","first_name":"Mikhail"},{"full_name":"Vlasov, Fedor","last_name":"Vlasov","first_name":"Fedor"},{"first_name":"Andrei","full_name":"Akopian, Andrei","last_name":"Akopian"},{"full_name":"Ratheesh, Aparna","last_name":"Ratheesh","orcid":"0000-0001-7190-0776","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","first_name":"Aparna"},{"full_name":"De Renzis, Stefano","last_name":"De Renzis","first_name":"Stefano"},{"full_name":"Siekhaus, Daria E","last_name":"Siekhaus","orcid":"0000-0001-8323-8353","first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"}],"project":[{"name":"Modeling epithelial tissue mechanics during cell invasion","call_identifier":"FWF","grant_number":"M02379","_id":"264CBBAC-B435-11E9-9278-68D0E5697425"}],"department":[{"_id":"DaSi"}],"isi":1,"day":"22","title":"Cell division in tissues enables macrophage infiltration","publication":"Science","acknowledged_ssus":[{"_id":"Bio"}],"publication_identifier":{"issn":["0036-8075"]},"article_processing_charge":"No","acknowledgement":"We thank J. Friml, C. Guet, T. Hurd, M. Fendrych and members of the laboratory for comments on the manuscript; the Bioimaging Facility of IST Austria for excellent support and T. Lecuit, E. Hafen, R. Levayer and A. Martin for fly strains. This work was supported by a grant from the Austrian Science Fund FWF: Lise Meitner Fellowship M2379-B28 to M.A and D.S., and internal funding from IST Austria to D.S. and EMBL to S.D.R.","status":"public","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2021.04.19.438995"}],"date_created":"2022-02-01T11:23:18Z"},{"issue":"8","publisher":"National Academy of Sciences","language":[{"iso":"eng"}],"doi":"10.1073/pnas.2122030119","date_published":"2022-02-14T00:00:00Z","oa":1,"file":[{"relation":"main_file","creator":"dernst","success":1,"date_created":"2022-02-21T08:45:11Z","content_type":"application/pdf","date_updated":"2022-02-21T08:45:11Z","file_size":1609678,"file_id":"10780","file_name":"2022_PNAS_Slovakova.pdf","access_level":"open_access","checksum":"d49f83c3580613966f71768ddb9a55a5"}],"article_type":"original","external_id":{"isi":["000766926900009"],"pmid":["35165179"]},"year":"2022","quality_controlled":"1","month":"02","scopus_import":"1","pmid":1,"tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"_id":"10766","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","volume":119,"type":"journal_article","corr_author":"1","citation":{"ieee":"J. Slovakova <i>et al.</i>, “Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 8. National Academy of Sciences, 2022.","apa":"Slovakova, J., Sikora, M. K., Arslan, F. N., Caballero Mancebo, S., Krens, G., Kaufmann, W., … Heisenberg, C.-P. J. (2022). Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2122030119\">https://doi.org/10.1073/pnas.2122030119</a>","ama":"Slovakova J, Sikora MK, Arslan FN, et al. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2022;119(8). doi:<a href=\"https://doi.org/10.1073/pnas.2122030119\">10.1073/pnas.2122030119</a>","short":"J. Slovakova, M.K. Sikora, F.N. Arslan, S. Caballero Mancebo, G. Krens, W. Kaufmann, J. Merrin, C.-P.J. Heisenberg, Proceedings of the National Academy of Sciences of the United States of America 119 (2022).","ista":"Slovakova J, Sikora MK, Arslan FN, Caballero Mancebo S, Krens G, Kaufmann W, Merrin J, Heisenberg C-PJ. 2022. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. Proceedings of the National Academy of Sciences of the United States of America. 119(8), e2122030119.","mla":"Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 8, e2122030119, National Academy of Sciences, 2022, doi:<a href=\"https://doi.org/10.1073/pnas.2122030119\">10.1073/pnas.2122030119</a>.","chicago":"Slovakova, Jana, Mateusz K Sikora, Feyza N Arslan, Silvia Caballero Mancebo, Gabriel Krens, Walter Kaufmann, Jack Merrin, and Carl-Philipp J Heisenberg. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2022. <a href=\"https://doi.org/10.1073/pnas.2122030119\">https://doi.org/10.1073/pnas.2122030119</a>."},"publication_status":"published","acknowledgement":"We thank Guillaume Salbreaux, Silvia Grigolon, Edouard Hannezo, and Vanessa Barone for discussions and comments on the manuscript and Shayan Shamipour and Daniel Capek for help with data analysis. We also thank the Imaging & Optics, Electron Microscopy, and Zebrafish Facility Scientific Service Units at the Institute of Science and Technology Austria (ISTA)Nasser Darwish-Miranda  for continuous support. We acknowledge Hitoshi Morita for the gift of VinculinB-GFP plasmid. This research was supported by an ISTA Fellow Marie-Curie Co-funding of regional, national, and international programmes Grant P_IST_EU01 (to J.S.), European Molecular Biology Organization Long-Term Fellowship Grant, ALTF reference number: 187-2013 (to M.S.), Schroedinger Fellowship J4332-B28 (to M.S.), and European Research Council Advanced Grant (MECSPEC; to C.-P.H.).","status":"public","file_date_updated":"2022-02-21T08:45:11Z","date_created":"2022-02-20T23:01:31Z","article_processing_charge":"No","publication_identifier":{"eissn":["1091-6490"]},"ec_funded":1,"related_material":{"record":[{"status":"public","relation":"earlier_version","id":"9750"}]},"publication":"Proceedings of the National Academy of Sciences of the United States of America","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"}],"day":"14","ddc":["570"],"title":"Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells","project":[{"name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734"},{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425"},{"name":"Modulation of adhesion function in cell-cell contact formation by cortical tension","grant_number":"187-2013","_id":"2521E28E-B435-11E9-9278-68D0E5697425"}],"department":[{"_id":"CaHe"},{"_id":"EM-Fac"},{"_id":"Bio"}],"isi":1,"has_accepted_license":"1","author":[{"id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87","first_name":"Jana","last_name":"Slovakova","full_name":"Slovakova, Jana"},{"full_name":"Sikora, Mateusz K","last_name":"Sikora","first_name":"Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Feyza N","id":"49DA7910-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5809-9566","last_name":"Arslan","full_name":"Arslan, Feyza N"},{"id":"2F1E1758-F248-11E8-B48F-1D18A9856A87","first_name":"Silvia","orcid":"0000-0002-5223-3346","last_name":"Caballero Mancebo","full_name":"Caballero Mancebo, Silvia"},{"last_name":"Krens","full_name":"Krens, Gabriel","id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel","orcid":"0000-0003-4761-5996"},{"orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","full_name":"Kaufmann, Walter","last_name":"Kaufmann"},{"first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609","last_name":"Merrin","full_name":"Merrin, Jack"},{"last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566"}],"abstract":[{"text":"Tension of the actomyosin cell cortex plays a key role in determining cell–cell contact growth and size. The level of cortical tension outside of the cell–cell contact, when pulling at the contact edge, scales with the total size to which a cell–cell contact can grow [J.-L. Maître et al., Science 338, 253–256 (2012)]. Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell–cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. After tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell–cell contact size is limited by tension-stabilizing E-cadherin–actin complexes at the contact.","lang":"eng"}],"intvolume":"       119","date_updated":"2026-04-02T12:54:56Z","article_number":"e2122030119","oa_version":"Published Version"},{"type":"journal_article","corr_author":"1","volume":1,"citation":{"short":"A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter, C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford Open Neuroscience 1 (2022).","ista":"Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM, Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 1(1), kvac009.","mla":"Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1, kvac009, Oxford University Press, 2022, doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>.","chicago":"Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>. Oxford University Press, 2022. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>.","ieee":"A. H. Hansen <i>et al.</i>, “Tissue-wide effects override cell-intrinsic gene function in radial neuron migration,” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1. Oxford University Press, 2022.","apa":"Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter, S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>","ama":"Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. 2022;1(1). doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>"},"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"10791","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"month":"07","pmid":1,"year":"2022","quality_controlled":"1","external_id":{"pmid":["38596707"]},"article_type":"original","issue":"1","publisher":"Oxford University Press","doi":"10.1093/oons/kvac009","date_published":"2022-07-07T00:00:00Z","language":[{"iso":"eng"}],"oa":1,"file":[{"access_level":"open_access","checksum":"822e76e056c07099d1fb27d1ece5941b","file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf","file_id":"14061","file_size":4846551,"date_updated":"2023-08-16T08:00:30Z","content_type":"application/pdf","date_created":"2023-08-16T08:00:30Z","success":1,"relation":"main_file","creator":"dernst"}],"abstract":[{"lang":"eng","text":"The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general."}],"date_updated":"2026-04-07T13:29:13Z","intvolume":"         1","article_number":"kvac009","oa_version":"Published Version","author":[{"last_name":"Hansen","full_name":"Hansen, Andi H","first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","orcid":"0000-0002-7462-0048"},{"full_name":"Riedl, Michael","last_name":"Riedl","orcid":"0000-0003-4844-6311","id":"3BE60946-F248-11E8-B48F-1D18A9856A87","first_name":"Michael"},{"last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"first_name":"Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","full_name":"Heger, Anna-Magdalena","last_name":"Heger"},{"last_name":"Laukoter","full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","first_name":"Susanne","orcid":"0000-0002-7903-3010"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"full_name":"Nicolas, Armel","last_name":"Nicolas","first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hof","full_name":"Hof, Björn","id":"3A374330-F248-11E8-B48F-1D18A9856A87","first_name":"Björn","orcid":"0000-0003-2057-2754"},{"last_name":"Tsai","full_name":"Tsai, Li Huei","first_name":"Li Huei"},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"}],"project":[{"name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425"},{"name":"Molecular mechanisms of radial neuronal migration","grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}],"department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"has_accepted_license":"1","day":"07","ddc":["570"],"title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","related_material":{"record":[{"status":"public","id":"12726","relation":"dissertation_contains"},{"relation":"dissertation_contains","id":"14530","status":"public"}]},"publication":"Oxford Open Neuroscience","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"publication_identifier":{"eissn":["2753-149X"]},"ec_funded":1,"article_processing_charge":"No","acknowledgement":"A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. This work also received support from IST Austria institutional funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer lab for discussion. This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics Facility, Lab Support Facility and Preclinical Facility.","file_date_updated":"2023-08-16T08:00:30Z","status":"public","date_created":"2022-02-25T07:52:11Z"},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 23, 1246–1255.","chicago":"Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>.","mla":"Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>.","short":"F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T. Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg, W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology 23 (2022) 1246–1255.","ieee":"F. P. Assen <i>et al.</i>, “Multitier mechanics control stromal adaptations in swelling lymph nodes,” <i>Nature Immunology</i>, vol. 23. Springer Nature, pp. 1246–1255, 2022.","ama":"Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. 2022;23:1246-1255. doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>","apa":"Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W., … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>"},"publication_status":"published","type":"journal_article","corr_author":"1","volume":23,"scopus_import":"1","month":"07","pmid":1,"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"_id":"9794","external_id":{"isi":["000822975900002"],"pmid":["35817845"]},"page":"1246-1255","year":"2022","quality_controlled":"1","oa":1,"file":[{"checksum":"628e7b49809f22c75b428842efe70c68","access_level":"open_access","file_name":"2022_NatureImmunology_Assen.pdf","file_id":"11642","file_size":11475325,"date_updated":"2022-07-25T07:11:32Z","content_type":"application/pdf","date_created":"2022-07-25T07:11:32Z","success":1,"creator":"dernst","relation":"main_file"}],"date_published":"2022-07-11T00:00:00Z","publisher":"Springer Nature","language":[{"iso":"eng"}],"doi":"10.1038/s41590-022-01257-4","article_type":"original","author":[{"orcid":"0000-0003-3470-6119","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","first_name":"Frank P","full_name":"Assen, Frank P","last_name":"Assen"},{"first_name":"Jun","last_name":"Abe","full_name":"Abe, Jun"},{"last_name":"Hons","full_name":"Hons, Miroslav","first_name":"Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348"},{"full_name":"Hauschild, Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert"},{"id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","first_name":"Shayan","full_name":"Shamipour, Shayan","last_name":"Shamipour"},{"last_name":"Kaufmann","full_name":"Kaufmann, Walter","first_name":"Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315"},{"last_name":"Costanzo","full_name":"Costanzo, Tommaso","first_name":"Tommaso","id":"D93824F4-D9BA-11E9-BB12-F207E6697425","orcid":"0000-0001-9732-3815"},{"full_name":"Krens, Gabriel","last_name":"Krens","orcid":"0000-0003-4761-5996","id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel"},{"last_name":"Brown","full_name":"Brown, Markus","first_name":"Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Burkhard","last_name":"Ludewig","full_name":"Ludewig, Burkhard"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon"},{"full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J"},{"first_name":"Wolfgang","full_name":"Weninger, Wolfgang","last_name":"Weninger"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","orcid":"0000-0001-6005-1561","last_name":"Hannezo","full_name":"Hannezo, Edouard B"},{"first_name":"Sanjiv A.","last_name":"Luther","full_name":"Luther, Sanjiv A."},{"first_name":"Jens V.","last_name":"Stein","full_name":"Stein, Jens V."},{"last_name":"Sixt","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-4561-241X"}],"intvolume":"        23","date_updated":"2025-06-11T13:52:43Z","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion."}],"title":"Multitier mechanics control stromal adaptations in swelling lymph nodes","day":"11","ddc":["570"],"has_accepted_license":"1","isi":1,"project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","call_identifier":"H2020","name":"Cellular Navigation Along Spatial Gradients"}],"department":[{"_id":"SiHi"},{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"MiSi"}],"ec_funded":1,"publication_identifier":{"issn":["1529-2908"],"eissn":["1529-2916"]},"publication":"Nature Immunology","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"LifeSc"}],"file_date_updated":"2022-07-25T07:11:32Z","status":"public","date_created":"2021-08-06T09:09:11Z","acknowledgement":"This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics, Electron Microscopy, Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing a custom 3D channel alignment script. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013.","article_processing_charge":"No"},{"keyword":["high ambient temperature","auxin","PINs","Zinc-Finger proteins","thermomorphogenesis","stress"],"file":[{"date_created":"2022-08-17T12:08:49Z","relation":"main_file","creator":"cartner","file_id":"11907","access_level":"open_access","checksum":"a2c2fdc28002538840490bfa6a08b2cb","embargo":"2023-09-08","file_name":"ChristinaArtner_PhD_Thesis_2022.pdf","date_updated":"2023-09-09T22:30:03Z","content_type":"application/pdf","file_size":11113608},{"date_updated":"2023-09-09T22:30:03Z","content_type":"application/octet-stream","file_size":19097730,"file_id":"11908","access_level":"closed","checksum":"66b461c074b815fbe63481b3f46a9f43","file_name":"ChristinaArtner_PhD_Thesis_2022.7z","embargo_to":"open_access","relation":"source_file","creator":"cartner","date_created":"2022-08-17T12:08:59Z"}],"oa":1,"date_published":"2022-08-17T00:00:00Z","language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria","doi":"10.15479/at:ista:11879","year":"2022","page":"128","_id":"11879","month":"08","publication_status":"published","supervisor":[{"last_name":"Benková","full_name":"Benková, Eva","id":"38F4F166-F248-11E8-B48F-1D18A9856A87","first_name":"Eva","orcid":"0000-0002-8510-9739"}],"citation":{"apa":"Artner, C. (2022). <i>Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11879\">https://doi.org/10.15479/at:ista:11879</a>","ama":"Artner C. Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11879\">10.15479/at:ista:11879</a>","ieee":"C. Artner, “Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature,” Institute of Science and Technology Austria, 2022.","short":"C. Artner, Modulation of Auxin Transport via ZF Proteins Adjust Plant Response to High Ambient Temperature, Institute of Science and Technology Austria, 2022.","chicago":"Artner, Christina. “Modulation of Auxin Transport via ZF Proteins Adjust Plant Response to High Ambient Temperature.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11879\">https://doi.org/10.15479/at:ista:11879</a>.","mla":"Artner, Christina. <i>Modulation of Auxin Transport via ZF Proteins Adjust Plant Response to High Ambient Temperature</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11879\">10.15479/at:ista:11879</a>.","ista":"Artner C. 2022. Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature. Institute of Science and Technology Austria."},"degree_awarded":"PhD","type":"dissertation","corr_author":"1","OA_place":"publisher","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","article_processing_charge":"No","date_created":"2022-08-17T07:58:53Z","file_date_updated":"2023-09-09T22:30:03Z","status":"public","acknowledgement":"I would like to acknowledge ISTA and all the people from the Scientific Service Units and at ISTA, in particular Dorota Jaworska for excellent technical and scientific support as well as ÖAW for funding my research for over 3 years (DOC ÖAW Fellowship PR1022OEAW02).","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"SSU"}],"publication_identifier":{"isbn":["978-3-99078-022-0"],"issn":["2663-337X"]},"has_accepted_license":"1","department":[{"_id":"GradSch"},{"_id":"EvBe"}],"project":[{"name":"Hormonal regulation of plant adaptive responses to environmental signals","_id":"2685A872-B435-11E9-9278-68D0E5697425"}],"title":"Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature","ddc":["580"],"alternative_title":["ISTA Thesis"],"day":"17","oa_version":"Published Version","date_updated":"2026-04-07T14:30:39Z","abstract":[{"lang":"eng","text":"As the overall global mean surface temperature is increasing due to climate change, plant\r\nadaptation to those stressful conditions is of utmost importance for their survival. Plants are\r\nsessile organisms, thus to compensate for their lack of mobility, they evolved a variety of\r\nmechanisms enabling them to flexibly adjust their physiological, growth and developmental\r\nprocesses to fluctuating temperatures and to survive in harsh environments. While these unique\r\nadaptation abilities provide an important evolutionary advantage, overall modulation of plant\r\ngrowth and developmental program due to non-optimal temperature negatively affects biomass\r\nproduction, crop productivity or sensitivity to pathogens. Thus, understanding molecular\r\nprocesses underlying plant adaptation to increased temperature can provide important\r\nresources for breeding strategies to ensure sufficient agricultural food production.\r\nAn increase in ambient temperature by a few degrees leads to profound changes in organ growth\r\nincluding enhanced hypocotyl elongation, expansion of petioles, hyponastic growth of leaves and\r\ncotyledons, collectively named thermomorphogenesis (Casal & Balasubramanian, 2019). Auxin,\r\none of the best-studied growth hormones, plays an essential role in this process by direct\r\nactivation of transcriptional and non-transcriptional processes resulting in elongation growth\r\n(Majda & Robert, 2018).To modulate hypocotyl growth in response to high ambient temperature\r\n(hAT), auxin needs to be redistributed accordingly. PINs, auxin efflux transporters, are key\r\ncomponents of the polar auxin transport (PAT) machinery, which controls the amount and\r\ndirection of auxin translocated in the plant tissues and organs(Adamowski & Friml, 2015). Hence,\r\nPIN-mediated transport is tightly linked with thermo-morphogenesis, and interference with PAT\r\nthrough either chemical or genetic means dramatically affecting the adaptive responses to hAT.\r\nIntriguingly, despite the key role of PIN mediated transport in growth response to hAT, whether\r\nand how PINs at the level of expression adapt to fluctuation in temperature is scarcely\r\nunderstood.\r\nWith genetic, molecular and advanced bio-imaging approaches, we demonstrate the role of PIN\r\nauxin transporters in the regulation of hypocotyl growth in response to hAT. We show that via\r\nadjustment of PIN3, PIN4 and PIN7 expression in cotyledons and hypocotyls, auxin distribution is modulated thereby determining elongation pattern of epidermal cells at hAT. Furthermore, we\r\nidentified three Zinc-Finger (ZF) transcription factors as novel molecular components of the\r\nthermo-regulatory network, which through negative regulation of PIN transcription adjust the\r\ntransport of auxin at hAT. Our results suggest that the ZF-PIN module might be a part of the\r\nnegative feedback loop attenuating the activity of the thermo-sensing pathway to restrain\r\nexaggerated growth and developmental responses to hAT."}],"author":[{"last_name":"Artner","full_name":"Artner, Christina","first_name":"Christina","id":"45DF286A-F248-11E8-B48F-1D18A9856A87"}]},{"author":[{"first_name":"Carlo Emanuele","full_name":"Villa, Carlo Emanuele","last_name":"Villa"},{"full_name":"Cheroni, Cristina","last_name":"Cheroni","first_name":"Cristina"},{"last_name":"Dotter","full_name":"Dotter, Christoph","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096"},{"last_name":"López-Tóbon","full_name":"López-Tóbon, Alejandro","first_name":"Alejandro"},{"last_name":"Oliveira","full_name":"Oliveira, Bárbara","first_name":"Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sacco","full_name":"Sacco, Roberto","first_name":"Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","full_name":"Yahya, Aysan Çerağ","last_name":"Yahya"},{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","full_name":"Morandell, Jasmin","last_name":"Morandell"},{"last_name":"Gabriele","full_name":"Gabriele, Michele","first_name":"Michele"},{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","first_name":"Mojtaba","orcid":"0000-0002-7667-6854","last_name":"Tavakoli","full_name":"Tavakoli, Mojtaba"},{"full_name":"Lyudchik, Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"full_name":"Gabitto, Mariano","last_name":"Gabitto","first_name":"Mariano"},{"full_name":"Danzl, Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Giuseppe","last_name":"Testa","full_name":"Testa, Giuseppe"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","last_name":"Novarino","full_name":"Novarino, Gaia"}],"intvolume":"        39","date_updated":"2026-07-01T22:30:05Z","oa_version":"Published Version","article_number":"110615","abstract":[{"text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.","lang":"eng"}],"title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","day":"05","ddc":["570"],"isi":1,"has_accepted_license":"1","project":[{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"_id":"2690FEAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I04205","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy"}],"department":[{"_id":"JoDa"},{"_id":"GaNo"}],"ec_funded":1,"publication_identifier":{"issn":["2211-1247"]},"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"18681"},{"status":"public","id":"18674","relation":"dissertation_contains"},{"id":"12364","relation":"dissertation_contains","status":"public"}]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"publication":"Cell Reports","status":"public","file_date_updated":"2022-04-15T09:06:25Z","date_created":"2022-04-15T09:03:10Z","acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com.","article_processing_charge":"Yes","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol. 39, no. 1, 110615, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>.","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>.","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. 2022;39(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>","ieee":"C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol. 39, no. 1. Elsevier, 2022."},"publication_status":"published","volume":39,"corr_author":"1","type":"journal_article","month":"04","scopus_import":"1","pmid":1,"_id":"11160","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"external_id":{"isi":["000785983900003"],"pmid":["35385734"]},"year":"2022","quality_controlled":"1","oa":1,"file":[{"file_id":"11164","checksum":"b4e8d68f0268dec499af333e6fd5d8e1","access_level":"open_access","file_name":"2022_CellReports_Villa.pdf","date_updated":"2022-04-15T09:06:25Z","content_type":"application/pdf","file_size":"7808644","date_created":"2022-04-15T09:06:25Z","relation":"main_file","creator":"dernst","success":1}],"issue":"1","doi":"10.1016/j.celrep.2022.110615","date_published":"2022-04-05T00:00:00Z","language":[{"iso":"eng"}],"publisher":"Elsevier","article_type":"original","keyword":["General Biochemistry","Genetics and Molecular Biology"]},{"acknowledgement":"We thank the scientific service units at ISTA, in particular M. Schunn’s team at the preclinical facility, and especially our colony manager S. Haslinger, for excellent support. We are also grateful to the ISTA Imaging & Optics Facility, and in particular C. Sommer for helping with the data file conversions. We thank R. Erhart from the ISTA Scientific Computing Unit for improving the script performance. We thank M. Maes, B. Nagy, S. Oakeley and M. Benevento and all members of the Siegert group for constant feedback on the project and on the manuscript. This research was supported by the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions program (754411 to R.J.A.C.), and by the European Research Council (grant no. 715571 to S.S.). L.K. was supported by funding to the Blue Brain Project, a research center of the École polytechnique fédérale de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology. L.-H.T. was supported by NIH (grant no. R37NS051874) and by the JPB Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.","date_created":"2023-01-16T09:53:07Z","file_date_updated":"2023-01-30T08:06:56Z","status":"public","article_processing_charge":"No","publication_identifier":{"eissn":["1546-1726"],"issn":["1097-6256"]},"ec_funded":1,"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}],"publication":"Nature Neuroscience","related_material":{"record":[{"status":"public","id":"12378","relation":"dissertation_contains"}],"link":[{"url":"https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/","relation":"press_release","description":"News on ISTA website"}]},"ddc":["570"],"day":"01","title":"A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes","department":[{"_id":"SaSi"}],"project":[{"name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"grant_number":"715571","call_identifier":"H2020","_id":"25D4A630-B435-11E9-9278-68D0E5697425","name":"Microglia action towards neuronal circuit formation and function in health and disease"}],"isi":1,"has_accepted_license":"1","author":[{"first_name":"Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","last_name":"Colombo","full_name":"Colombo, Gloria"},{"id":"850B2E12-9CD4-11E9-837F-E719E6697425","first_name":"Ryan J","orcid":"0000-0003-0002-1867","last_name":"Cubero","full_name":"Cubero, Ryan J"},{"full_name":"Kanari, Lida","last_name":"Kanari","first_name":"Lida"},{"full_name":"Venturino, Alessandro","last_name":"Venturino","orcid":"0000-0003-2356-9403","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Schulz","full_name":"Schulz, Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","first_name":"Rouven","orcid":"0000-0001-5297-733X"},{"first_name":"Martina","last_name":"Scolamiero","full_name":"Scolamiero, Martina"},{"last_name":"Agerberg","full_name":"Agerberg, Jens","first_name":"Jens"},{"first_name":"Hansruedi","last_name":"Mathys","full_name":"Mathys, Hansruedi"},{"last_name":"Tsai","full_name":"Tsai, Li-Huei","first_name":"Li-Huei"},{"first_name":"Wojciech","full_name":"Chachólski, Wojciech","last_name":"Chachólski"},{"full_name":"Hess, Kathryn","last_name":"Hess","first_name":"Kathryn"},{"full_name":"Siegert, Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra"}],"abstract":[{"lang":"eng","text":"Environmental cues influence the highly dynamic morphology of microglia. Strategies to characterize these changes usually involve user-selected morphometric features, which preclude the identification of a spectrum of context-dependent morphological phenotypes. Here we develop MorphOMICs, a topological data analysis approach, which enables semiautomatic mapping of microglial morphology into an atlas of cue-dependent phenotypes and overcomes feature-selection biases and biological variability. We extract spatially heterogeneous and sexually dimorphic morphological phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines with maturation but increases over the disease trajectories in two neurodegeneration mouse models, with females showing a faster morphological shift in affected brain regions. Remarkably, microglia morphologies reflect an adaptation upon repeated exposure to ketamine anesthesia and do not recover to control morphologies. Finally, we demonstrate that both long primary processes and short terminal processes provide distinct insights to morphological phenotypes. MorphOMICs opens a new perspective to characterize microglial morphology."}],"oa_version":"Published Version","date_updated":"2026-07-01T22:30:09Z","intvolume":"        25","publisher":"Springer Nature","doi":"10.1038/s41593-022-01167-6","date_published":"2022-10-01T00:00:00Z","language":[{"iso":"eng"}],"issue":"10","file":[{"content_type":"application/pdf","date_updated":"2023-01-30T08:06:56Z","file_size":23789835,"file_id":"12437","file_name":"2022_NatureNeuroscience_Colombo.pdf","checksum":"28431146873096f52e0107b534f178c9","access_level":"open_access","creator":"dernst","relation":"main_file","success":1,"date_created":"2023-01-30T08:06:56Z"}],"oa":1,"keyword":["General Neuroscience"],"article_type":"original","page":"1379-1393","external_id":{"pmid":["36180790"],"isi":["000862214700001"]},"quality_controlled":"1","year":"2022","pmid":1,"month":"10","scopus_import":"1","_id":"12244","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","corr_author":"1","volume":25,"type":"journal_article","publication_status":"published","citation":{"ama":"Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. 2022;25(10):1379-1393. doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>","apa":"Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero, M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>","ieee":"G. Colombo <i>et al.</i>, “A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes,” <i>Nature Neuroscience</i>, vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022.","mla":"Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>, vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>.","chicago":"Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>.","ista":"Colombo G, Cubero RJ, Kanari L, Venturino A, Schulz R, Scolamiero M, Agerberg J, Mathys H, Tsai L-H, Chachólski W, Hess K, Siegert S. 2022. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. Nature Neuroscience. 25(10), 1379–1393.","short":"G. Colombo, R.J. Cubero, L. Kanari, A. Venturino, R. Schulz, M. Scolamiero, J. Agerberg, H. Mathys, L.-H. Tsai, W. Chachólski, K. Hess, S. Siegert, Nature Neuroscience 25 (2022) 1379–1393."}},{"abstract":[{"text":"Environmental cues influence the highly dynamic morphology of microglia. Strategies to \r\ncharacterize these changes usually involve user-selected morphometric features, which \r\npreclude the identification of a spectrum of context-dependent morphological phenotypes. \r\nHere, we develop MorphOMICs, a topological data analysis approach, which enables semi\u0002automatic mapping of microglial morphology into an atlas of cue-dependent phenotypes,\r\novercomes feature-selection bias and minimizes biological variability. \r\nFirst, with MorphOMICs we derive the morphological spectrum of microglia across seven \r\nbrain regions during postnatal development and in two distinct Alzheimer’s disease \r\ndegeneration mouse models. We uncover region-specific and sexually dimorphic\r\nmorphological trajectories, with females showing an earlier morphological shift than males in \r\nthe degenerating brain. Overall, we demonstrate that both long primary- and short terminal \r\nprocesses provide distinct insights to morphological phenotypes. Moreover, using machine \r\nlearning to map novel condition on the spectrum, we observe that microglia morphologies \r\nreflect a dose-dependent adaptation upon ketamine anesthesia and do not recover to control \r\nmorphologies.\r\nNext, we took advantage of MorphOMICs to build a high-resolution and layer-specific map of \r\nmicroglial morphological spectrum in the retina, covering postnatal development and rd10 \r\ndegeneration. Here, following photoreceptor death, microglia assume an early development\u0002like morphology. Finally, we map microglial morphology following optic nerve crush on the \r\nretinal spectrum and observe a layer- and sex-dependent response. \r\nOverall, MorphOMICs opens a new perspective to analyze microglial morphology across \r\nmultiple conditions, and provides a novel tool to characterize microglial morphology beyond \r\nthe traditionally dichotomized view of microglia.","lang":"eng"}],"date_updated":"2026-04-07T14:29:41Z","oa_version":"Published Version","author":[{"first_name":"Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","last_name":"Colombo","full_name":"Colombo, Gloria"}],"project":[{"call_identifier":"H2020","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program"}],"department":[{"_id":"GradSch"},{"_id":"SaSi"}],"has_accepted_license":"1","day":"11","alternative_title":["ISTA Thesis"],"ddc":["570"],"title":"MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}],"related_material":{"record":[{"id":"12244","relation":"part_of_dissertation","status":"public"}]},"publication_identifier":{"issn":["2663-337X"]},"ec_funded":1,"article_processing_charge":"No","status":"public","file_date_updated":"2023-04-12T22:30:03Z","date_created":"2023-01-25T14:27:43Z","corr_author":"1","type":"dissertation","degree_awarded":"PhD","citation":{"ista":"Colombo G. 2022. MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes. Institute of Science and Technology Austria.","chicago":"Colombo, Gloria. “MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:12378\">https://doi.org/10.15479/at:ista:12378</a>.","mla":"Colombo, Gloria. <i>MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:12378\">10.15479/at:ista:12378</a>.","short":"G. Colombo, MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes, Institute of Science and Technology Austria, 2022.","ama":"Colombo G. MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:12378\">10.15479/at:ista:12378</a>","apa":"Colombo, G. (2022). <i>MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12378\">https://doi.org/10.15479/at:ista:12378</a>","ieee":"G. Colombo, “MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes,” Institute of Science and Technology Austria, 2022."},"supervisor":[{"orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","full_name":"Siegert, Sandra","last_name":"Siegert"}],"publication_status":"published","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"_id":"12378","month":"11","year":"2022","page":"142","doi":"10.15479/at:ista:12378","language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria","date_published":"2022-11-11T00:00:00Z","oa":1,"file":[{"creator":"cchlebak","relation":"source_file","date_created":"2023-01-25T14:31:32Z","file_size":23890382,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2023-04-12T22:30:03Z","file_name":"Gloria_Colombo_Thesis.docx","embargo_to":"open_access","checksum":"8cd3ddfe9b53381dcf086023d8d8893a","access_level":"closed","file_id":"12379"},{"relation":"main_file","creator":"cchlebak","date_created":"2023-01-25T14:31:36Z","file_size":13802421,"date_updated":"2023-04-12T22:30:03Z","content_type":"application/pdf","access_level":"open_access","embargo":"2023-04-11","checksum":"8af4319c18b516e8758e9a6cb02b103b","file_name":"Gloria_Colombo_Thesis.pdf","file_id":"12380"}]},{"author":[{"first_name":"Florian","last_name":"Gaertner","full_name":"Gaertner, Florian"},{"orcid":"0000-0003-1681-508X","id":"26E95904-5160-11E9-9C0B-C5B0DC97E90F","first_name":"Patricia","full_name":"Dos Reis Rodrigues, Patricia","last_name":"Dos Reis Rodrigues"},{"full_name":"De Vries, Ingrid","last_name":"De Vries","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid"},{"first_name":"Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","last_name":"Hons","full_name":"Hons, Miroslav"},{"last_name":"Aguilera","full_name":"Aguilera, Juan","first_name":"Juan"},{"last_name":"Riedl","full_name":"Riedl, Michael","first_name":"Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4844-6311"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F","orcid":"0000-0002-1073-744X","last_name":"Leithner","full_name":"Leithner, Alexander F"},{"orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren","full_name":"Tasciyan, Saren","last_name":"Tasciyan"},{"orcid":"0000-0002-2187-6656","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","first_name":"Aglaja","full_name":"Kopf, Aglaja","last_name":"Kopf"},{"orcid":"0000-0001-5145-4609","first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","full_name":"Merrin, Jack","last_name":"Merrin"},{"last_name":"Zheden","full_name":"Zheden, Vanessa","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","first_name":"Vanessa","orcid":"0000-0002-9438-4783"},{"first_name":"Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","last_name":"Kaufmann","full_name":"Kaufmann, Walter"},{"first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","last_name":"Hauschild","full_name":"Hauschild, Robert"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","last_name":"Sixt","full_name":"Sixt, Michael K"}],"abstract":[{"text":"When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.","lang":"eng"}],"oa_version":"Published Version","intvolume":"        57","date_updated":"2026-07-01T22:30:14Z","ddc":["570"],"day":"10","title":"WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues","department":[{"_id":"MiSi"},{"_id":"EM-Fac"},{"_id":"NanoFab"},{"_id":"BjHo"}],"project":[{"_id":"260AA4E2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"747687","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells"},{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","call_identifier":"H2020","name":"Cellular Navigation Along Spatial Gradients"}],"isi":1,"publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]},"ec_funded":1,"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"20149"},{"relation":"dissertation_contains","id":"12726","status":"public"},{"id":"14530","relation":"dissertation_contains","status":"public"},{"id":"12401","relation":"dissertation_contains","status":"public"}]},"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"publication":"Developmental Cell","acknowledgement":"We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll for advice on fluorescent labeling of collagen gels. This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron Microscopy Facility. This work was funded by grants from the European Research Council ( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 747687.","main_file_link":[{"open_access":"1","url":"https://www.sciencedirect.com/science/article/pii/S1534580721009497"}],"date_created":"2022-01-30T23:01:33Z","status":"public","article_processing_charge":"No","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","corr_author":"1","type":"journal_article","volume":57,"publication_status":"published","citation":{"chicago":"Gaertner, Florian, Patricia Dos Reis Rodrigues, Ingrid de Vries, Miroslav Hons, Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” <i>Developmental Cell</i>. 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FtsA allegedly initiates cell division by switching from an inactive polymeric to an active monomeric confirmation, which recruits downstream proteins and stabilizes FtsZ filaments. Here, we use biochemical reconstitution experiments combined with quantitative fluorescence microscopy to study divisome activation in vitro. We compare wildtype-FtsA with FtsA-R286W, a constantly active gain-of-function mutant and find that R286W outperforms the wildtype protein in replicating FtsZ treadmilling dynamics, stabilizing FtsZ filaments and recruiting FtsN. We attribute these differences to a faster membrane exchange of FtsA-R286W and its higher packing density below FtsZ filaments.  Using FRET microscopy, we find that FtsN binding does not compete with, but promotes FtsA self-interaction. Our findings suggest a model where FtsA always forms dynamic polymers on the membrane, which re-organize during assembly and activation of the divisome. 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This work was supported by the European Research Council through grant ERC 2015-StG-679239 and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L. and HFSP LT 000824/2016-L4 to N.B. For the purpose of open access, we have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.","contributor":[{"contributor_type":"supervisor","last_name":"Loose","orcid":"0000-0001-7309-9724","first_name":"Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87"},{"contributor_type":"researcher","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"first_name":"Paulo","contributor_type":"researcher","last_name":"Caldas"},{"contributor_type":"researcher","last_name":"Michalik","id":"B9577E20-AA38-11E9-AC9A-0930E6697425","first_name":"David"},{"contributor_type":"researcher","last_name":"Baranova","first_name":"Natalia"}],"related_material":{"link":[{"url":"https://doi.org/10.5281/zenodo.6400639","description":"A custom written code (FRAPdiff) to quantify the Off binding rate and Diffusion coefficient of membrane bound proteins. Written by Christoph Sommer.","relation":"software"}],"record":[{"id":"11373","relation":"used_in_publication","status":"public"},{"relation":"used_in_publication","id":"14280","status":"public"}]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"ec_funded":1},{"scopus_import":"1","month":"05","_id":"11373","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","volume":13,"corr_author":"1","type":"journal_article","citation":{"short":"P. Radler, N.S. Baranova, P.R. Dos Santos Caldas, C.M. Sommer, M.D. Lopez Pelegrin, D. Michalik, M. Loose, Nature Communications 13 (2022).","ista":"Radler P, Baranova NS, Dos Santos Caldas PR, Sommer CM, Lopez Pelegrin MD, Michalik D, Loose M. 2022. In vitro reconstitution of Escherichia coli divisome activation. Nature Communications. 13, 2635.","mla":"Radler, Philipp, et al. “In Vitro Reconstitution of Escherichia Coli Divisome Activation.” <i>Nature Communications</i>, vol. 13, 2635, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-30301-y\">10.1038/s41467-022-30301-y</a>.","chicago":"Radler, Philipp, Natalia S. Baranova, Paulo R Dos Santos Caldas, Christoph M Sommer, Maria D Lopez Pelegrin, David Michalik, and Martin Loose. “In Vitro Reconstitution of Escherichia Coli Divisome Activation.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-30301-y\">https://doi.org/10.1038/s41467-022-30301-y</a>.","ieee":"P. Radler <i>et al.</i>, “In vitro reconstitution of Escherichia coli divisome activation,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","ama":"Radler P, Baranova NS, Dos Santos Caldas PR, et al. In vitro reconstitution of Escherichia coli divisome activation. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-30301-y\">10.1038/s41467-022-30301-y</a>","apa":"Radler, P., Baranova, N. S., Dos Santos Caldas, P. R., Sommer, C. M., Lopez Pelegrin, M. D., Michalik, D., &#38; Loose, M. (2022). In vitro reconstitution of Escherichia coli divisome activation. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-30301-y\">https://doi.org/10.1038/s41467-022-30301-y</a>"},"publication_status":"published","language":[{"iso":"eng"}],"doi":"10.1038/s41467-022-30301-y","publisher":"Springer Nature","date_published":"2022-05-12T00:00:00Z","oa":1,"file":[{"date_updated":"2022-05-13T09:10:51Z","content_type":"application/pdf","file_size":6945191,"file_id":"11374","access_level":"open_access","checksum":"5af863ee1b95a0710f6ee864d68dc7a6","file_name":"2022_NatureCommunications_Radler.pdf","relation":"main_file","creator":"dernst","success":1,"date_created":"2022-05-13T09:10:51Z"}],"keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry"],"article_type":"original","external_id":{"isi":["000795171100037"]},"year":"2022","quality_controlled":"1","day":"12","ddc":["570"],"title":"In vitro reconstitution of Escherichia coli divisome activation","project":[{"_id":"2595697A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"679239","name":"Self-Organization of the Bacterial Cell"},{"name":"In vitro reconstitution of bacterial cell division","_id":"fc38323b-9c52-11eb-aca3-ff8afb4a011d","grant_number":"P34607"}],"department":[{"_id":"MaLo"}],"isi":1,"has_accepted_license":"1","author":[{"id":"40136C2A-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","orcid":"0000-0001-9198-2182 ","last_name":"Radler","full_name":"Radler, Philipp"},{"id":"38661662-F248-11E8-B48F-1D18A9856A87","first_name":"Natalia S.","orcid":"0000-0002-3086-9124","last_name":"Baranova","full_name":"Baranova, Natalia S."},{"orcid":"0000-0001-6730-4461","first_name":"Paulo R","id":"38FCDB4C-F248-11E8-B48F-1D18A9856A87","full_name":"Dos Santos Caldas, Paulo R","last_name":"Dos Santos Caldas"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"id":"319AA9CE-F248-11E8-B48F-1D18A9856A87","first_name":"Maria D","last_name":"Lopez Pelegrin","full_name":"Lopez Pelegrin, Maria D"},{"id":"B9577E20-AA38-11E9-AC9A-0930E6697425","first_name":"David","last_name":"Michalik","full_name":"Michalik, David"},{"full_name":"Loose, Martin","last_name":"Loose","orcid":"0000-0001-7309-9724","id":"462D4284-F248-11E8-B48F-1D18A9856A87","first_name":"Martin"}],"abstract":[{"text":"The actin-homologue FtsA is essential for E. coli cell division, as it links FtsZ filaments in the Z-ring to transmembrane proteins. FtsA is thought to initiate cell constriction by switching from an inactive polymeric to an active monomeric conformation, which recruits downstream proteins and stabilizes the Z-ring. However, direct biochemical evidence for this mechanism is missing. Here, we use reconstitution experiments and quantitative fluorescence microscopy to study divisome activation in vitro. By comparing wild-type FtsA with FtsA R286W, we find that this hyperactive mutant outperforms FtsA WT in replicating FtsZ treadmilling dynamics, FtsZ filament stabilization and recruitment of FtsN. We could attribute these differences to a faster exchange and denser packing of FtsA R286W below FtsZ filaments. Using FRET microscopy, we also find that FtsN binding promotes FtsA self-interaction. We propose that in the active divisome FtsA and FtsN exist as a dynamic copolymer that follows treadmilling filaments of FtsZ.","lang":"eng"}],"date_updated":"2026-07-01T22:30:15Z","intvolume":"        13","article_number":"2635","oa_version":"Published Version","acknowledgement":"We acknowledge members of the Loose laboratory at IST Austria for helpful discussions—in particular L. Lindorfer for his assistance with cloning and purifications. We thank J. Löwe and T. Nierhaus (MRC-LMB Cambridge, UK) for sharing unpublished work and helpful discussions, as well as D. Vavylonis and D. Rutkowski (Lehigh University, Bethlehem, PA, USA) and S. Martin (University of Lausanne, Switzerland) for sharing their code for FRAP analysis. We are also thankful for the support by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging and Optics Facility (IOF) and the Lab Support Facility (LSF). This work was supported by the European Research Council through grant ERC 2015-StG-679239 and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L. and HFSP LT 000824/2016-L4 to N.B. For the purpose of open access, we have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.","status":"public","file_date_updated":"2022-05-13T09:10:51Z","date_created":"2022-05-13T09:06:28Z","article_processing_charge":"No","publication_identifier":{"issn":["2041-1723"]},"ec_funded":1,"publication":"Nature Communications","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41467-022-34485-1"}],"record":[{"relation":"research_data","id":"10934","status":"public"},{"id":"14280","relation":"dissertation_contains","status":"public"}]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}]},{"abstract":[{"lang":"eng","text":"Growth regulation tailors development in plants to their environment. A prominent example of this is the response to gravity, in which shoots bend up and roots bend down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic engineering and phosphoproteomics in Arabidopsis thaliana, we advance understanding of how auxin inhibits root growth. We show that auxin activates two distinct, antagonistically acting signalling pathways that converge on rapid regulation of apoplastic pH, a causative determinant of growth. Cell surface-based TRANSMEMBRANE KINASE1 (TMK1) interacts with and mediates phosphorylation and activation of plasma membrane H+-ATPases for apoplast acidification, while intracellular canonical auxin signalling promotes net cellular H+ influx, causing apoplast alkalinization. Simultaneous activation of these two counteracting mechanisms poises roots for rapid, fine-tuned growth modulation in navigating complex soil environments."}],"oa_version":"Preprint","intvolume":"       599","date_updated":"2025-07-10T11:49:46Z","author":[{"first_name":"Lanxin","id":"367EF8FA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5607-272X","last_name":"Li","full_name":"Li, Lanxin"},{"last_name":"Verstraeten","full_name":"Verstraeten, Inge","first_name":"Inge","id":"362BF7FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7241-2328"},{"first_name":"Mark","last_name":"Roosjen","full_name":"Roosjen, Mark"},{"last_name":"Takahashi","full_name":"Takahashi, Koji","first_name":"Koji"},{"last_name":"Rodriguez Solovey","full_name":"Rodriguez Solovey, Lesia","first_name":"Lesia","id":"3922B506-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7244-7237"},{"first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609","last_name":"Merrin","full_name":"Merrin, Jack"},{"first_name":"Jian","last_name":"Chen","full_name":"Chen, Jian"},{"last_name":"Shabala","full_name":"Shabala, Lana","first_name":"Lana"},{"full_name":"Smet, Wouter","last_name":"Smet","first_name":"Wouter"},{"full_name":"Ren, Hong","last_name":"Ren","first_name":"Hong"},{"full_name":"Vanneste, Steffen","last_name":"Vanneste","first_name":"Steffen"},{"full_name":"Shabala, Sergey","last_name":"Shabala","first_name":"Sergey"},{"first_name":"Bert","full_name":"De Rybel, Bert","last_name":"De Rybel"},{"first_name":"Dolf","last_name":"Weijers","full_name":"Weijers, Dolf"},{"first_name":"Toshinori","full_name":"Kinoshita, Toshinori","last_name":"Kinoshita"},{"first_name":"William M.","last_name":"Gray","full_name":"Gray, William M."},{"last_name":"Friml","full_name":"Friml, Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","first_name":"Jiří","orcid":"0000-0002-8302-7596"}],"department":[{"_id":"JiFr"},{"_id":"NanoFab"}],"project":[{"_id":"261099A6-B435-11E9-9278-68D0E5697425","grant_number":"742985","call_identifier":"H2020","name":"Tracing Evolution of Auxin Transport and Polarity in Plants"},{"name":"Molecular mechanisms of endocytic cargo recognition in plants","grant_number":"I03630","call_identifier":"FWF","_id":"26538374-B435-11E9-9278-68D0E5697425"},{"name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385"},{"name":"A Case Study of Plant Growth Regulation: Molecular Mechanism of Auxin-mediated Rapid Growth Inhibition in Arabidopsis Root","_id":"26B4D67E-B435-11E9-9278-68D0E5697425","grant_number":"25351"}],"isi":1,"day":"11","title":"Cell surface and intracellular auxin signalling for H<sup>+</sup> fluxes in root growth","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"Bio"}],"publication":"Nature","related_material":{"link":[{"relation":"press_release","description":"News on IST Webpage","url":"https://ist.ac.at/en/news/stop-and-grow/"}],"record":[{"status":"public","id":"10095","relation":"earlier_version"}]},"publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"ec_funded":1,"article_processing_charge":"No","acknowledgement":"We thank N. Gnyliukh and L. Hörmayer for technical assistance and N. Paris for sharing PM-Cyto seeds. We gratefully acknowledge the Life Science, Machine Shop and Bioimaging Facilities of IST Austria. This project has received funding from the European Research Council Advanced Grant (ETAP-742985) and the Austrian Science Fund (FWF) under I 3630-B25 to J.F., the National Institutes of Health (GM067203) to W.M.G., the Netherlands Organization for Scientific Research (NWO; VIDI-864.13.001), Research Foundation-Flanders (FWO; Odysseus II G0D0515N) and a European Research Council Starting Grant (TORPEDO-714055) to W.S. and B.D.R., the VICI grant (865.14.001) from the Netherlands Organization for Scientific Research to M.R. and D.W., the Australian Research Council and China National Distinguished Expert Project (WQ20174400441) to S.S., the MEXT/JSPS KAKENHI to K.T. (20K06685) and T.K. (20H05687 and 20H05910), the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement no. 665385 and the DOC Fellowship of the Austrian Academy of Sciences to L.L., and the China Scholarship Council to J.C.","date_created":"2021-11-07T23:01:25Z","main_file_link":[{"url":"https://www.doi.org/10.21203/rs.3.rs-266395/v3","open_access":"1"}],"status":"public","type":"journal_article","corr_author":"1","volume":599,"publication_status":"published","citation":{"ieee":"L. Li <i>et al.</i>, “Cell surface and intracellular auxin signalling for H<sup>+</sup> fluxes in root growth,” <i>Nature</i>, vol. 599, no. 7884. Springer Nature, pp. 273–277, 2021.","apa":"Li, L., Verstraeten, I., Roosjen, M., Takahashi, K., Rodriguez Solovey, L., Merrin, J., … Friml, J. (2021). Cell surface and intracellular auxin signalling for H<sup>+</sup> fluxes in root growth. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-021-04037-6\">https://doi.org/10.1038/s41586-021-04037-6</a>","ama":"Li L, Verstraeten I, Roosjen M, et al. Cell surface and intracellular auxin signalling for H<sup>+</sup> fluxes in root growth. <i>Nature</i>. 2021;599(7884):273-277. doi:<a href=\"https://doi.org/10.1038/s41586-021-04037-6\">10.1038/s41586-021-04037-6</a>","short":"L. Li, I. Verstraeten, M. Roosjen, K. Takahashi, L. Rodriguez Solovey, J. Merrin, J. Chen, L. Shabala, W. Smet, H. Ren, S. Vanneste, S. Shabala, B. De Rybel, D. Weijers, T. Kinoshita, W.M. Gray, J. Friml, Nature 599 (2021) 273–277.","mla":"Li, Lanxin, et al. “Cell Surface and Intracellular Auxin Signalling for H<sup>+</sup> Fluxes in Root Growth.” <i>Nature</i>, vol. 599, no. 7884, Springer Nature, 2021, pp. 273–77, doi:<a href=\"https://doi.org/10.1038/s41586-021-04037-6\">10.1038/s41586-021-04037-6</a>.","chicago":"Li, Lanxin, Inge Verstraeten, Mark Roosjen, Koji Takahashi, Lesia Rodriguez Solovey, Jack Merrin, Jian Chen, et al. “Cell Surface and Intracellular Auxin Signalling for H<sup>+</sup> Fluxes in Root Growth.” <i>Nature</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41586-021-04037-6\">https://doi.org/10.1038/s41586-021-04037-6</a>.","ista":"Li L, Verstraeten I, Roosjen M, Takahashi K, Rodriguez Solovey L, Merrin J, Chen J, Shabala L, Smet W, Ren H, Vanneste S, Shabala S, De Rybel B, Weijers D, Kinoshita T, Gray WM, Friml J. 2021. Cell surface and intracellular auxin signalling for H<sup>+</sup> fluxes in root growth. Nature. 599(7884), 273–277."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"10223","pmid":1,"scopus_import":"1","month":"11","quality_controlled":"1","year":"2021","page":"273-277","external_id":{"isi":["000713338100006"],"pmid":["34707283"]},"keyword":["Multidisciplinary"],"article_type":"original","publisher":"Springer Nature","doi":"10.1038/s41586-021-04037-6","date_published":"2021-11-11T00:00:00Z","language":[{"iso":"eng"}],"issue":"7884","oa":1},{"citation":{"mla":"Hörmayer, Lukas, et al. “Automated Time-Lapse Imaging and Manipulation of Cell Divisions in Arabidopsis Roots by Vertical-Stage Confocal Microscopy.” <i>Plant Cell Division</i>, vol. 2382, Humana Press, 2021, pp. 105–14, doi:<a href=\"https://doi.org/10.1007/978-1-0716-1744-1_6\">10.1007/978-1-0716-1744-1_6</a>.","chicago":"Hörmayer, Lukas, Jiří Friml, and Matous Glanc. “Automated Time-Lapse Imaging and Manipulation of Cell Divisions in Arabidopsis Roots by Vertical-Stage Confocal Microscopy.” In <i>Plant Cell Division</i>, 2382:105–14. MIMB. Humana Press, 2021. <a href=\"https://doi.org/10.1007/978-1-0716-1744-1_6\">https://doi.org/10.1007/978-1-0716-1744-1_6</a>.","ista":"Hörmayer L, Friml J, Glanc M. 2021.Automated time-lapse imaging and manipulation of cell divisions in Arabidopsis roots by vertical-stage confocal microscopy. In: Plant Cell Division. Methods in Molecular Biology, vol. 2382, 105–114.","short":"L. Hörmayer, J. Friml, M. Glanc, in:, Plant Cell Division, Humana Press, 2021, pp. 105–114.","ama":"Hörmayer L, Friml J, Glanc M. Automated time-lapse imaging and manipulation of cell divisions in Arabidopsis roots by vertical-stage confocal microscopy. In: <i>Plant Cell Division</i>. Vol 2382. MIMB. Humana Press; 2021:105-114. doi:<a href=\"https://doi.org/10.1007/978-1-0716-1744-1_6\">10.1007/978-1-0716-1744-1_6</a>","apa":"Hörmayer, L., Friml, J., &#38; Glanc, M. (2021). Automated time-lapse imaging and manipulation of cell divisions in Arabidopsis roots by vertical-stage confocal microscopy. In <i>Plant Cell Division</i> (Vol. 2382, pp. 105–114). Humana Press. <a href=\"https://doi.org/10.1007/978-1-0716-1744-1_6\">https://doi.org/10.1007/978-1-0716-1744-1_6</a>","ieee":"L. Hörmayer, J. Friml, and M. Glanc, “Automated time-lapse imaging and manipulation of cell divisions in Arabidopsis roots by vertical-stage confocal microscopy,” in <i>Plant Cell Division</i>, vol. 2382, Humana Press, 2021, pp. 105–114."},"publication_status":"published","type":"book_chapter","volume":2382,"series_title":"MIMB","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"10268","month":"10","scopus_import":"1","pmid":1,"year":"2021","quality_controlled":"1","external_id":{"pmid":["34705235"]},"page":"105-114","date_published":"2021-10-28T00:00:00Z","publisher":"Humana Press","language":[{"iso":"eng"}],"doi":"10.1007/978-1-0716-1744-1_6","date_updated":"2022-06-03T06:47:06Z","intvolume":"      2382","oa_version":"None","abstract":[{"text":"The analysis of dynamic cellular processes such as plant cytokinesis stands and falls with live-cell time-lapse confocal imaging. Conventional approaches to time-lapse imaging of cell division in Arabidopsis root tips are tedious and have low throughput. Here, we describe a protocol for long-term time-lapse simultaneous imaging of multiple root tips on a vertical-stage confocal microscope with automated root tracking. We also provide modifications of the basic protocol to implement this imaging method in the analysis of genetic, pharmacological or laser ablation wounding-mediated experimental manipulations. Our method dramatically improves the efficiency of cell division time-lapse imaging by increasing the throughput, while reducing the person-hour requirements of such experiments.","lang":"eng"}],"author":[{"id":"2EEE7A2A-F248-11E8-B48F-1D18A9856A87","first_name":"Lukas","full_name":"Hörmayer, Lukas","last_name":"Hörmayer"},{"first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","last_name":"Friml","full_name":"Friml, Jiří"},{"full_name":"Glanc, Matous","last_name":"Glanc","orcid":"0000-0003-0619-7783","id":"1AE1EA24-02D0-11E9-9BAA-DAF4881429F2","first_name":"Matous"}],"department":[{"_id":"JiFr"}],"title":"Automated time-lapse imaging and manipulation of cell divisions in Arabidopsis roots by vertical-stage confocal microscopy","day":"28","alternative_title":["Methods in Molecular Biology"],"acknowledged_ssus":[{"_id":"Bio"}],"publication":"Plant Cell Division","publication_identifier":{"eisbn":["978-1-0716-1744-1"],"issn":["1064-3745"],"isbn":["978-1-0716-1743-4"],"eissn":["1940-6029"]},"article_processing_charge":"No","status":"public","date_created":"2021-11-11T10:03:30Z","acknowledgement":"We thank B. De Rybel for allowing M.G. to work on this manuscript during a postdoc in his laboratory, and EMBO for supporting M.G. with a Long-Term fellowship (ALTF 1005-2019) during this time. We acknowledge the service and support by the Bioimaging Facility at IST Austria, and finally, we thank A. Mally for proofreading and correcting the manuscript."}]