[{"_id":"10791","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","ddc":["570"],"date_updated":"2023-11-30T10:55:12Z","file_date_updated":"2023-08-16T08:00:30Z","department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"oa_version":"Published Version","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."}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"intvolume":" 1","month":"07","language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"checksum":"822e76e056c07099d1fb27d1ece5941b","file_id":"14061","file_size":4846551,"date_updated":"2023-08-16T08:00:30Z","creator":"dernst","file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf","date_created":"2023-08-16T08:00:30Z"}],"publication_status":"published","publication_identifier":{"eissn":["2753-149X"]},"ec_funded":1,"issue":"1","related_material":{"record":[{"relation":"dissertation_contains","id":"12726","status":"public"},{"status":"public","id":"14530","relation":"dissertation_contains"}]},"volume":1,"article_number":"kvac009","project":[{"name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444","_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.” Oxford Open Neuroscience. Oxford Academic, 2022. https://doi.org/10.1093/oons/kvac009.","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.” Oxford Open Neuroscience, vol. 1, no. 1, kvac009, Oxford Academic, 2022, doi:10.1093/oons/kvac009.","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).","ieee":"A. H. Hansen et al., “Tissue-wide effects override cell-intrinsic gene function in radial neuron migration,” Oxford Open Neuroscience, vol. 1, no. 1. Oxford Academic, 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. Oxford Open Neuroscience. Oxford Academic. https://doi.org/10.1093/oons/kvac009","ama":"Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 2022;1(1). doi:10.1093/oons/kvac009"},"title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","article_processing_charge":"No","author":[{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","last_name":"Hansen","full_name":"Hansen, Andi H"},{"full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian"},{"full_name":"Riedl, Michael","orcid":"0000-0003-4844-6311","last_name":"Riedl","first_name":"Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","full_name":"Streicher, Carmen"},{"last_name":"Heger","full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","first_name":"Anna-Magdalena"},{"full_name":"Laukoter, Susanne","orcid":"0000-0002-7903-3010","last_name":"Laukoter","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","first_name":"Susanne"},{"orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","last_name":"Nicolas"},{"first_name":"Björn","id":"3A374330-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2057-2754","full_name":"Hof, Björn","last_name":"Hof"},{"full_name":"Tsai, Li Huei","last_name":"Tsai","first_name":"Li Huei"},{"first_name":"Thomas","full_name":"Rülicke, Thomas","last_name":"Rülicke"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"}],"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.","oa":1,"quality_controlled":"1","publisher":"Oxford Academic","publication":"Oxford Open Neuroscience","day":"07","year":"2022","has_accepted_license":"1","date_created":"2022-02-25T07:52:11Z","doi":"10.1093/oons/kvac009","date_published":"2022-07-07T00:00:00Z"},{"title":"Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling","external_id":{"isi":["000706409200006"]},"article_processing_charge":"Yes","author":[{"last_name":"Artan","orcid":"0000-0001-8945-6992","full_name":"Artan, Murat","id":"C407B586-6052-11E9-B3AE-7006E6697425","first_name":"Murat"},{"first_name":"Stephen","id":"57740d2b-2a88-11ec-97cf-d9e6d1b39677","full_name":"Barratt, Stephen","last_name":"Barratt"},{"first_name":"Sean M.","full_name":"Flynn, Sean M.","last_name":"Flynn"},{"first_name":"Farida","last_name":"Begum","full_name":"Begum, Farida"},{"first_name":"Mark","full_name":"Skehel, Mark","last_name":"Skehel"},{"full_name":"Nicolas, Armel","last_name":"Nicolas","first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","first_name":"Mario","full_name":"De Bono, Mario","orcid":"0000-0001-8347-0443","last_name":"De Bono"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"apa":"Artan, M., Barratt, S., Flynn, S. M., Begum, F., Skehel, M., Nicolas, A., & de Bono, M. (2021). Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling. Journal of Biological Chemistry. Elsevier. https://doi.org/10.1016/J.JBC.2021.101094","ama":"Artan M, Barratt S, Flynn SM, et al. Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling. Journal of Biological Chemistry. 2021;297(3). doi:10.1016/J.JBC.2021.101094","short":"M. Artan, S. Barratt, S.M. Flynn, F. Begum, M. Skehel, A. Nicolas, M. de Bono, Journal of Biological Chemistry 297 (2021).","ieee":"M. Artan et al., “Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling,” Journal of Biological Chemistry, vol. 297, no. 3. Elsevier, 2021.","mla":"Artan, Murat, et al. “Interactome Analysis of Caenorhabditis Elegans Synapses by TurboID-Based Proximity Labeling.” Journal of Biological Chemistry, vol. 297, no. 3, 101094, Elsevier, 2021, doi:10.1016/J.JBC.2021.101094.","ista":"Artan M, Barratt S, Flynn SM, Begum F, Skehel M, Nicolas A, de Bono M. 2021. Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling. Journal of Biological Chemistry. 297(3), 101094.","chicago":"Artan, Murat, Stephen Barratt, Sean M. Flynn, Farida Begum, Mark Skehel, Armel Nicolas, and Mario de Bono. “Interactome Analysis of Caenorhabditis Elegans Synapses by TurboID-Based Proximity Labeling.” Journal of Biological Chemistry. Elsevier, 2021. https://doi.org/10.1016/J.JBC.2021.101094."},"project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"}],"article_number":"101094","date_created":"2021-10-10T22:01:23Z","doi":"10.1016/J.JBC.2021.101094","date_published":"2021-09-01T00:00:00Z","publication":"Journal of Biological Chemistry","day":"01","year":"2021","has_accepted_license":"1","isi":1,"oa":1,"publisher":"Elsevier","quality_controlled":"1","acknowledgement":"We thank de Bono lab members for helpful comments on the manuscript, IST Austria and University of Vienna Mass Spec Facilities for invaluable discussions and comments for the optimization of mass spec analyses of worm samples. The biotin auxotropic E. coli strain MG1655bioB:kan was gift from John Cronan (University of Illinois) and was kindly sent to us by Jessica Feldman and Ariana Sanchez (Stanford University). dg398 pEntryslot2_mNeongreen::3XFLAG::stop and dg397 pEntryslot3_mNeongreen::3XFLAG::stop::unc-54 3′UTR entry vector were kindly shared by Dr Dominique Glauser (University of Fribourg). Codon-optimized mScarlet vector was a generous gift from Dr Manuel Zimmer (University of Vienna).","department":[{"_id":"MaDe"},{"_id":"LifeSc"}],"file_date_updated":"2021-10-11T12:20:58Z","ddc":["612"],"date_updated":"2023-08-14T07:24:09Z","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","_id":"10117","ec_funded":1,"issue":"3","volume":297,"language":[{"iso":"eng"}],"file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"19e39d36c5b9387c6dc0e89c9ae856ab","file_id":"10121","success":1,"creator":"cchlebak","date_updated":"2021-10-11T12:20:58Z","file_size":1680010,"date_created":"2021-10-11T12:20:58Z","file_name":"2021_JBC_Artan.pdf"}],"publication_status":"published","publication_identifier":{"eissn":["1083-351X"],"issn":["0021-9258"]},"intvolume":" 297","month":"09","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Proximity labeling provides a powerful in vivo tool to characterize the proteome of subcellular structures and the interactome of specific proteins. The nematode Caenorhabditis elegans is one of the most intensely studied organisms in biology, offering many advantages for biochemistry. Using the highly active biotin ligase TurboID, we optimize here a proximity labeling protocol for C. elegans. An advantage of TurboID is that biotin's high affinity for streptavidin means biotin-labeled proteins can be affinity-purified under harsh denaturing conditions. By combining extensive sonication with aggressive denaturation using SDS and urea, we achieved near-complete solubilization of worm proteins. We then used this protocol to characterize the proteomes of the worm gut, muscle, skin, and nervous system. Neurons are among the smallest C. elegans cells. To probe the method's sensitivity, we expressed TurboID exclusively in the two AFD neurons and showed that the protocol could identify known and previously unknown proteins expressed selectively in AFD. The active zones of synapses are composed of a protein matrix that is difficult to solubilize and purify. To test if our protocol could solubilize active zone proteins, we knocked TurboID into the endogenous elks-1 gene, which encodes a presynaptic active zone protein. We identified many known ELKS-1-interacting active zone proteins, as well as previously uncharacterized synaptic proteins. Versatile vectors and the inherent advantages of using C. elegans, including fast growth and the ability to rapidly make and functionally test knock-ins, make proximity labeling a valuable addition to the armory of this model organism."}]},{"quality_controlled":"1","publisher":"Springer Nature","oa":1,"acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","doi":"10.1038/s41467-021-23123-x","date_published":"2021-05-24T00:00:00Z","date_created":"2021-05-28T11:49:46Z","has_accepted_license":"1","isi":1,"year":"2021","day":"24","publication":"Nature Communications","project":[{"name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"F07807","name":"Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"}],"article_number":"3058","author":[{"first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell","full_name":"Morandell, Jasmin"},{"full_name":"Schwarz, Lena A","last_name":"Schwarz","first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","last_name":"Basilico","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"last_name":"Tasciyan","full_name":"Tasciyan, Saren","orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren"},{"orcid":"0000-0001-8370-6161","full_name":"Dimchev, Georgi A","last_name":"Dimchev","first_name":"Georgi A","id":"38C393BE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Nicolas, Armel","last_name":"Nicolas","first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline","last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline"},{"first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","last_name":"Dotter"},{"last_name":"Knaus","full_name":"Knaus, Lisa","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","full_name":"Dobler, Zoe","last_name":"Dobler"},{"full_name":"Cacci, Emanuele","last_name":"Cacci","first_name":"Emanuele"},{"first_name":"Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078","last_name":"Schur"},{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","external_id":{"isi":["000658769900010"]},"title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","citation":{"mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x.","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23123-x","ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"05","intvolume":" 12","abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs."}],"acknowledged_ssus":[{"_id":"PreCl"}],"oa_version":"Published Version","issue":"1","volume":12,"related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/"}],"record":[{"id":"7800","status":"public","relation":"earlier_version"},{"relation":"dissertation_contains","status":"public","id":"12401"}]},"ec_funded":1,"publication_identifier":{"eissn":["2041-1723"]},"publication_status":"published","file":[{"creator":"kschuh","date_updated":"2021-05-28T12:39:43Z","file_size":9358599,"date_created":"2021-05-28T12:39:43Z","file_name":"2021_NatureCommunications_Morandell.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"337e0f7959c35ec959984cacdcb472ba","file_id":"9430","success":1}],"language":[{"iso":"eng"}],"article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","keyword":["General Biochemistry","Genetics and Molecular Biology"],"_id":"9429","department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"file_date_updated":"2021-05-28T12:39:43Z","date_updated":"2024-03-27T23:30:23Z","ddc":["572"]},{"publisher":"Cold Spring Harbor Laboratory","oa":1,"has_accepted_license":"1","year":"2020","day":"11","publication":"bioRxiv","doi":"10.1101/2020.01.10.902064 ","date_published":"2020-01-11T00:00:00Z","date_created":"2020-05-05T14:31:33Z","project":[{"grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"}],"citation":{"ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” bioRxiv. Cold Spring Harbor Laboratory.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.).","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. doi:10.1101/2020.01.10.902064 ","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.01.10.902064 ","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.01.10.902064 .","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, 10.1101/2020.01.10.902064 .","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.01.10.902064 ."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Morandell, Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin"},{"first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Lena A","last_name":"Schwarz"},{"id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette","full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","last_name":"Basilico"},{"first_name":"Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","last_name":"Tasciyan"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel","full_name":"Nicolas, Armel","last_name":"Nicolas"},{"full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline","full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger"},{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa","full_name":"Knaus, Lisa","last_name":"Knaus"},{"first_name":"Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","full_name":"Dobler, Zoe","last_name":"Dobler"},{"last_name":"Cacci","full_name":"Cacci, Emanuele","first_name":"Emanuele"},{"last_name":"Danzl","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"}],"article_processing_charge":"No","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","acknowledged_ssus":[{"_id":"PreCl"}],"abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages."}],"oa_version":"Preprint","month":"01","publication_status":"submitted","file":[{"date_created":"2020-05-05T14:31:19Z","file_name":"2020.01.10.902064v1.full.pdf","creator":"rsix","date_updated":"2020-07-14T12:48:03Z","file_size":2931370,"file_id":"7801","checksum":"c6799ab5daba80efe8e2ed63c15f8c81","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"later_version","status":"public","id":"9429"},{"status":"public","id":"8620","relation":"dissertation_contains"}]},"_id":"7800","type":"preprint","tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"status":"public","date_updated":"2024-03-27T23:30:14Z","ddc":["570"],"department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"file_date_updated":"2020-07-14T12:48:03Z"},{"oa_version":"Published Version","pmid":1,"abstract":[{"text":"Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome.","lang":"eng"}],"month":"08","intvolume":" 12","scopus_import":1,"file":[{"checksum":"4a2bb7994b7f2c432bf44f5127ea3102","file_id":"6829","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2019_BMC_Antoniou.pdf","date_created":"2019-08-23T11:10:35Z","creator":"dernst","file_size":1177482,"date_updated":"2020-07-14T12:47:40Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1756-0500"]},"publication_status":"published","volume":12,"related_material":{"record":[{"status":"public","id":"9784","relation":"research_data"}]},"_id":"6819","status":"public","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570"],"date_updated":"2023-02-23T14:08:14Z","file_date_updated":"2020-07-14T12:47:40Z","department":[{"_id":"LifeSc"}],"publisher":"BioMed Central","quality_controlled":"1","oa":1,"day":"08","publication":"BMC Research Notes","has_accepted_license":"1","year":"2019","date_published":"2019-08-08T00:00:00Z","doi":"10.1186/s13104-019-4534-3","date_created":"2019-08-18T22:00:39Z","article_number":"494","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Antoniou, Michael N., et al. “Glyphosate Does Not Substitute for Glycine in Proteins of Actively Dividing Mammalian Cells.” BMC Research Notes, vol. 12, 494, BioMed Central, 2019, doi:10.1186/s13104-019-4534-3.","apa":"Antoniou, M. N., Nicolas, A., Mesnage, R., Biserni, M., Rao, F. V., & Martin, C. V. (2019). Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells. BMC Research Notes. BioMed Central. https://doi.org/10.1186/s13104-019-4534-3","ama":"Antoniou MN, Nicolas A, Mesnage R, Biserni M, Rao FV, Martin CV. Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells. BMC Research Notes. 2019;12. doi:10.1186/s13104-019-4534-3","ieee":"M. N. Antoniou, A. Nicolas, R. Mesnage, M. Biserni, F. V. Rao, and C. V. Martin, “Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells,” BMC Research Notes, vol. 12. BioMed Central, 2019.","short":"M.N. Antoniou, A. Nicolas, R. Mesnage, M. Biserni, F.V. Rao, C.V. Martin, BMC Research Notes 12 (2019).","chicago":"Antoniou, Michael N., Armel Nicolas, Robin Mesnage, Martina Biserni, Francesco V. Rao, and Cristina Vazquez Martin. “Glyphosate Does Not Substitute for Glycine in Proteins of Actively Dividing Mammalian Cells.” BMC Research Notes. BioMed Central, 2019. https://doi.org/10.1186/s13104-019-4534-3.","ista":"Antoniou MN, Nicolas A, Mesnage R, Biserni M, Rao FV, Martin CV. 2019. Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells. BMC Research Notes. 12, 494."},"title":"Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells","author":[{"last_name":"Antoniou","full_name":"Antoniou, Michael N.","first_name":"Michael N."},{"full_name":"Nicolas, Armel","last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel"},{"first_name":"Robin","full_name":"Mesnage, Robin","last_name":"Mesnage"},{"last_name":"Biserni","full_name":"Biserni, Martina","first_name":"Martina"},{"first_name":"Francesco V.","full_name":"Rao, Francesco V.","last_name":"Rao"},{"first_name":"Cristina Vazquez","full_name":"Martin, Cristina Vazquez","last_name":"Martin"}],"article_processing_charge":"No","external_id":{"pmid":["31395095"]}},{"day":"09","year":"2019","date_published":"2019-08-09T00:00:00Z","doi":"10.6084/m9.figshare.9411761.v1","related_material":{"record":[{"status":"public","id":"6819","relation":"used_in_publication"}]},"date_created":"2021-08-06T08:14:05Z","oa_version":"Published Version","abstract":[{"text":"Additional file 1: Table S1. Kinetics of MDA-MB-231 cell growth in either the presence or absence of 100Â mg/L glyphosate. Cell counts are given at day-1 of seeding flasks and following 6-days of continuous culture. Note: no differences in cell numbers were observed between negative control and glyphosate treated cultures.","lang":"eng"}],"month":"08","publisher":"Springer Nature","main_file_link":[{"url":"https://doi.org/10.6084/m9.figshare.9411761.v1","open_access":"1"}],"oa":1,"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","citation":{"ista":"Antoniou MN, Nicolas A, Mesnage R, Biserni M, Rao FV, Martin CV. 2019. MOESM1 of Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells, Springer Nature, 10.6084/m9.figshare.9411761.v1.","chicago":"Antoniou, Michael N., Armel Nicolas, Robin Mesnage, Martina Biserni, Francesco V. Rao, and Cristina Vazquez Martin. “MOESM1 of Glyphosate Does Not Substitute for Glycine in Proteins of Actively Dividing Mammalian Cells.” Springer Nature, 2019. https://doi.org/10.6084/m9.figshare.9411761.v1.","ieee":"M. N. Antoniou, A. Nicolas, R. Mesnage, M. Biserni, F. V. Rao, and C. V. Martin, “MOESM1 of Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells.” Springer Nature, 2019.","short":"M.N. Antoniou, A. Nicolas, R. Mesnage, M. Biserni, F.V. Rao, C.V. Martin, (2019).","apa":"Antoniou, M. N., Nicolas, A., Mesnage, R., Biserni, M., Rao, F. V., & Martin, C. V. (2019). MOESM1 of Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells. Springer Nature. https://doi.org/10.6084/m9.figshare.9411761.v1","ama":"Antoniou MN, Nicolas A, Mesnage R, Biserni M, Rao FV, Martin CV. MOESM1 of Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells. 2019. doi:10.6084/m9.figshare.9411761.v1","mla":"Antoniou, Michael N., et al. MOESM1 of Glyphosate Does Not Substitute for Glycine in Proteins of Actively Dividing Mammalian Cells. Springer Nature, 2019, doi:10.6084/m9.figshare.9411761.v1."},"date_updated":"2023-02-23T12:52:29Z","title":"MOESM1 of Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells","department":[{"_id":"LifeSc"}],"author":[{"full_name":"Antoniou, Michael N.","last_name":"Antoniou","first_name":"Michael N."},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel","last_name":"Nicolas","full_name":"Nicolas, Armel"},{"first_name":"Robin","last_name":"Mesnage","full_name":"Mesnage, Robin"},{"full_name":"Biserni, Martina","last_name":"Biserni","first_name":"Martina"},{"full_name":"Rao, Francesco V.","last_name":"Rao","first_name":"Francesco V."},{"first_name":"Cristina Vazquez","full_name":"Martin, Cristina Vazquez","last_name":"Martin"}],"article_processing_charge":"No","_id":"9784","status":"public","type":"research_data_reference"},{"citation":{"mla":"Morandell, Jasmin, et al. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology, vol. 29, no. Supplement 6, Elsevier, 2019, pp. S11–12, doi:10.1016/j.euroneuro.2019.09.040.","short":"J. Morandell, A. Nicolas, L.A. Schwarz, G. Novarino, European Neuropsychopharmacology 29 (2019) S11–S12.","ieee":"J. Morandell, A. Nicolas, L. A. Schwarz, and G. Novarino, “S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism,” European Neuropsychopharmacology, vol. 29, no. Supplement 6. Elsevier, pp. S11–S12, 2019.","apa":"Morandell, J., Nicolas, A., Schwarz, L. A., & Novarino, G. (2019). S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.040","ama":"Morandell J, Nicolas A, Schwarz LA, Novarino G. S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. 2019;29(Supplement 6):S11-S12. doi:10.1016/j.euroneuro.2019.09.040","chicago":"Morandell, Jasmin, Armel Nicolas, Lena A Schwarz, and Gaia Novarino. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology. Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.040.","ista":"Morandell J, Nicolas A, Schwarz LA, Novarino G. 2019. S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. 29(Supplement 6), S11–S12."},"date_updated":"2023-09-07T14:56:17Z","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","external_id":{"isi":["000502657500021"]},"article_processing_charge":"No","author":[{"last_name":"Morandell","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel","last_name":"Nicolas","full_name":"Nicolas, Armel"},{"first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","full_name":"Schwarz, Lena A"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"title":"S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism","department":[{"_id":"GaNo"},{"_id":"LifeSc"}],"_id":"7415","article_type":"original","type":"journal_article","status":"public","year":"2019","publication_status":"published","publication_identifier":{"issn":["0924-977X"]},"isi":1,"publication":"European Neuropsychopharmacology","language":[{"iso":"eng"}],"day":"13","page":"S11-S12","date_created":"2020-01-30T10:07:41Z","issue":"Supplement 6","date_published":"2019-12-13T00:00:00Z","volume":29,"doi":"10.1016/j.euroneuro.2019.09.040","oa_version":"None","publisher":"Elsevier","quality_controlled":"1","intvolume":" 29","month":"12"}]