[{"PlanS_conform":"1","abstract":[{"text":"Circadian clocks underlie daily rhythms in physiology by coordinating temporal patterns of gene expression and protein function throughout the body. At the core of this system in mammals is CLOCK/BMAL1, a ubiquitously expressed heterodimeric transcription factor complex that orchestrates tissue-specific circadian gene expression. The basis for this specificity remains unclear, but tissue-specific interactions at chromatin could provide one. Here we used chromatin immunoprecipitation coupled to mass spectrometry to map CLOCK/BMAL1-associated protein complexes on chromatin in mouse liver, kidney and lung. We detected 1,510 associated proteins, most of which were tissue-specific and not explained by protein abundance. Among these, we identified the homeodomain transcription factors PROX1, HNF1B and HOXA5 as tissue-enriched interactors that bind BMAL1, co-occupy most BMAL1 genomic sites and establish organ-restricted circadian transcription. Our findings demonstrate that tissue-specific transcription factors confer cellular identity on the core clock, thereby contributing to organ-specific patterns of rhythmic gene expression.","lang":"eng"}],"project":[{"_id":"9136c684-16d5-11f0-9cad-91c0177b365f","grant_number":"101162145","name":"Circadian structural transitions of chromatin"}],"title":"CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators","external_id":{"pmid":["42562924"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","dataavailabilitystatement":"Proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE64 partner repository with the dataset identifiers PXD062751 and PXD077567. RNA-seq data are available in the European Nucleotide Archive (ENA) under accession no. PRJEB93884, and ChIP–seq data at the Gene Expression Omnibus (GEO) under accession no. GSE302237. AlphaFold 3 interaction prediction parameters can be provided during the revision process on editorial and/or review request. Source data are provided with this paper.","scopus_import":"1","year":"2026","day":"06","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"status":"public","date_updated":"2026-08-18T08:03:22Z","OA_place":"publisher","acknowledgement":"We thank all members of the Robles’ group for critical comments on and edits to this paper. We thank S. Kay for providing dihXY HCC cell lines and D. Firsov and Y. Bignon for mouse BMAL1-knockout (KO) kidney tissues. This work was supported by the German Research Foundation (DFG) project no. 213249687—SFB 1064 and RO 5675/1-1 to M.S.R., F.A. and L.A.H. M.S.R was also supported by DFG INST 86/1800-1 FUGG and LMU Munich’s Institutional Strategy LMU excellent within the framework of the German Excellence Initiative. J.S.M. was supported by US National Institutes of Health grant nos. R01GM145737 and R01DK128133. A.K.M. was supported by an ERC grant ‘ChromaChrono’ 101162145. Open access funding provided by Ludwig-Maximilians-Universität München.","quality_controlled":"1","month":"08","type":"journal_article","_id":"22720","doi":"10.1038/s41556-026-02041-4","article_processing_charge":"Yes (via OA deal)","publication":"Nature Cell Biology","has_accepted_license":"1","article_type":"original","das_tickbox":"1","publication_status":"epub_ahead","date_created":"2026-08-16T22:01:44Z","supplementarymaterial":"yes","pmid":1,"author":[{"full_name":"Aygenli, Fatih","last_name":"Aygenli","first_name":"Fatih"},{"last_name":"Huschet","full_name":"Huschet, Lukas A.","first_name":"Lukas A."},{"full_name":"Popp, Tanja","last_name":"Popp","first_name":"Tanja"},{"first_name":"Andrea","last_name":"Ribeiro","full_name":"Ribeiro, Andrea"},{"full_name":"Barkhatova, Darina","last_name":"Barkhatova","orcid":"0000-0002-0062-2817","id":"db547c8c-329f-11ee-a353-cde802618f9e","first_name":"Darina"},{"first_name":"Céline","full_name":"Jouffe, Céline","last_name":"Jouffe"},{"first_name":"Ricardo","full_name":"Trozzo, Ricardo","last_name":"Trozzo"},{"last_name":"Menet","full_name":"Menet, Jerome S.","first_name":"Jerome S."},{"last_name":"Rad","full_name":"Rad, Roland","first_name":"Roland"},{"last_name":"Dyar","full_name":"Dyar, Kenneth A.","first_name":"Kenneth A."},{"last_name":"Lech","full_name":"Lech, Maciej","first_name":"Maciej"},{"full_name":"Straub, Tobias","last_name":"Straub","first_name":"Tobias"},{"first_name":"Alicia","id":"6437c950-2a03-11ee-914d-d6476dd7b75c","orcid":"0000-0002-6080-839X","last_name":"Michael","full_name":"Michael, Alicia"},{"last_name":"Robles","full_name":"Robles, Maria S.","first_name":"Maria S."}],"language":[{"iso":"eng"}],"oa":1,"oa_version":"Published Version","department":[{"_id":"GradSch"},{"_id":"AlMi"}],"publication_identifier":{"issn":["1465-7392"],"eissn":["1476-4679"]},"OA_type":"hybrid","date_published":"2026-08-06T00:00:00Z","ddc":["570"],"main_file_link":[{"url":"https://doi.org/10.1038/s41556-026-02041-4","open_access":"1"}],"publisher":"Springer Nature","citation":{"ama":"Aygenli F, Huschet LA, Popp T, et al. CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators. <i>Nature Cell Biology</i>. 2026. doi:<a href=\"https://doi.org/10.1038/s41556-026-02041-4\">10.1038/s41556-026-02041-4</a>","short":"F. Aygenli, L.A. Huschet, T. Popp, A. Ribeiro, D. Barkhatova, C. Jouffe, R. Trozzo, J.S. Menet, R. Rad, K.A. Dyar, M. Lech, T. Straub, A.K. Michael, M.S. Robles, Nature Cell Biology (2026).","ista":"Aygenli F, Huschet LA, Popp T, Ribeiro A, Barkhatova D, Jouffe C, Trozzo R, Menet JS, Rad R, Dyar KA, Lech M, Straub T, Michael AK, Robles MS. 2026. CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators. Nature Cell Biology.","chicago":"Aygenli, Fatih, Lukas A. Huschet, Tanja Popp, Andrea Ribeiro, Darina Barkhatova, Céline Jouffe, Ricardo Trozzo, et al. “CLOCK/BMAL1 Interactome Uncovers Homeodomain Factors as Tissue Regulators.” <i>Nature Cell Biology</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41556-026-02041-4\">https://doi.org/10.1038/s41556-026-02041-4</a>.","ieee":"F. Aygenli <i>et al.</i>, “CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators,” <i>Nature Cell Biology</i>. Springer Nature, 2026.","apa":"Aygenli, F., Huschet, L. A., Popp, T., Ribeiro, A., Barkhatova, D., Jouffe, C., … Robles, M. S. (2026). CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators. <i>Nature Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41556-026-02041-4\">https://doi.org/10.1038/s41556-026-02041-4</a>","mla":"Aygenli, Fatih, et al. “CLOCK/BMAL1 Interactome Uncovers Homeodomain Factors as Tissue Regulators.” <i>Nature Cell Biology</i>, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41556-026-02041-4\">10.1038/s41556-026-02041-4</a>."},"researchdata_availability":"yes"},{"_id":"9629","type":"journal_article","month":"06","quality_controlled":"1","acknowledgement":"We acknowledge the members of the Lennon-Duménil laboratory for sharing the mouse line of Myh9-GFP. We are grateful to the members of the Liberali laboratory and the FMI facilities for their support. We thank E. Tagliavini for IT support; L. Gelman for assistance and training; S. Bichet and A. Bogucki for helping with histology of mouse tissues; H. Kohler for fluorescence-activated cell sorting; G. Q. G. de Medeiros for maintenance of light-sheet microscopy; M. G. Stadler for scRNA-seq analysis; G. Gay for discussions on the 3D vertex model; the members of the Liberali laboratory, C. P. Heisenberg and C. Tsiairis for reading and providing feedback on the manuscript. Funding: Q.Y. is supported by a Postdoc fellowship from Peter und Taul Engelhorn Stiftung (PTES). This work received funding from the European Research Council (ERC) under the EU Horizon 2020 research and Innovation Programme Grant Agreement no. 758617 (to P.L.), the Swiss National Foundation (SNF) (POOP3_157531, to P.L.) and from the ERC under the EU Horizon 2020 Research and Innovation Program Grant Agreements 851288 (to E.H.) and the Austrian Science Fund (FWF) (P31639, to E.H.).","volume":23,"date_updated":"2025-04-14T07:52:26Z","status":"public","day":"21","year":"2021","scopus_import":"1","external_id":{"isi":["000664016300003"],"pmid":["34155381"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Cell fate coordinates mechano-osmotic forces in intestinal crypt formation","project":[{"call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis","grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E"},{"grant_number":"P31639","name":"Active mechano-chemical description of the cell cytoskeleton","call_identifier":"FWF","_id":"268294B6-B435-11E9-9278-68D0E5697425"}],"abstract":[{"lang":"eng","text":"Intestinal organoids derived from single cells undergo complex crypt–villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis."}],"page":"733–744","corr_author":"1","citation":{"ama":"Yang Q, Xue S, Chan CJ, et al. Cell fate coordinates mechano-osmotic forces in intestinal crypt formation. <i>Nature Cell Biology</i>. 2021;23:733–744. doi:<a href=\"https://doi.org/10.1038/s41556-021-00700-2\">10.1038/s41556-021-00700-2</a>","ista":"Yang Q, Xue S, Chan CJ, Rempfler M, Vischi D, Maurer-Gutierrez F, Hiiragi T, Hannezo EB, Liberali P. 2021. Cell fate coordinates mechano-osmotic forces in intestinal crypt formation. Nature Cell Biology. 23, 733–744.","short":"Q. Yang, S. Xue, C.J. Chan, M. Rempfler, D. Vischi, F. Maurer-Gutierrez, T. Hiiragi, E.B. Hannezo, P. Liberali, Nature Cell Biology 23 (2021) 733–744.","chicago":"Yang, Qiutan, Shi-lei Xue, Chii Jou Chan, Markus Rempfler, Dario Vischi, Francisca Maurer-Gutierrez, Takashi Hiiragi, Edouard B Hannezo, and Prisca Liberali. “Cell Fate Coordinates Mechano-Osmotic Forces in Intestinal Crypt Formation.” <i>Nature Cell Biology</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41556-021-00700-2\">https://doi.org/10.1038/s41556-021-00700-2</a>.","ieee":"Q. Yang <i>et al.</i>, “Cell fate coordinates mechano-osmotic forces in intestinal crypt formation,” <i>Nature Cell Biology</i>, vol. 23. Springer Nature, pp. 733–744, 2021.","apa":"Yang, Q., Xue, S., Chan, C. J., Rempfler, M., Vischi, D., Maurer-Gutierrez, F., … Liberali, P. (2021). Cell fate coordinates mechano-osmotic forces in intestinal crypt formation. <i>Nature Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41556-021-00700-2\">https://doi.org/10.1038/s41556-021-00700-2</a>","mla":"Yang, Qiutan, et al. “Cell Fate Coordinates Mechano-Osmotic Forces in Intestinal Crypt Formation.” <i>Nature Cell Biology</i>, vol. 23, Springer Nature, 2021, pp. 733–744, doi:<a href=\"https://doi.org/10.1038/s41556-021-00700-2\">10.1038/s41556-021-00700-2</a>."},"publisher":"Springer Nature","date_published":"2021-06-21T00:00:00Z","main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/2020.05.13.094359","open_access":"1"}],"publication_identifier":{"issn":["1465-7392"],"eissn":["1476-4679"]},"department":[{"_id":"EdHa"}],"oa_version":"Preprint","oa":1,"language":[{"iso":"eng"}],"author":[{"first_name":"Qiutan","last_name":"Yang","full_name":"Yang, Qiutan"},{"first_name":"Shi-lei","id":"31D2C804-F248-11E8-B48F-1D18A9856A87","last_name":"Xue","full_name":"Xue, Shi-lei"},{"full_name":"Chan, Chii Jou","last_name":"Chan","first_name":"Chii Jou"},{"first_name":"Markus","last_name":"Rempfler","full_name":"Rempfler, Markus"},{"full_name":"Vischi, Dario","last_name":"Vischi","first_name":"Dario"},{"first_name":"Francisca","last_name":"Maurer-Gutierrez","full_name":"Maurer-Gutierrez, Francisca"},{"first_name":"Takashi","last_name":"Hiiragi","full_name":"Hiiragi, Takashi"},{"last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","first_name":"Edouard B"},{"first_name":"Prisca","last_name":"Liberali","full_name":"Liberali, Prisca"}],"pmid":1,"date_created":"2021-07-04T22:01:25Z","publication_status":"published","article_type":"original","intvolume":"        23","isi":1,"publication":"Nature Cell Biology","ec_funded":1,"article_processing_charge":"No","doi":"10.1038/s41556-021-00700-2"},{"title":"Migrasomes take center stage","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"isi":["000478029000003"],"pmid":["31371826"]},"scopus_import":"1","year":"2019","day":"01","status":"public","page":"918-920","abstract":[{"text":"Migrasomes are a recently discovered type of extracellular vesicles that are characteristically generated along retraction fibers in migrating cells. Two studies now show how migrasomes are formed and how they function in the physiologically relevant context of the developing zebrafish embryo.","lang":"eng"}],"month":"08","issue":"8","type":"journal_article","_id":"6837","date_updated":"2023-08-29T07:42:20Z","volume":21,"quality_controlled":"1","date_created":"2019-09-01T22:00:57Z","pmid":1,"language":[{"iso":"eng"}],"author":[{"first_name":"Ste","full_name":"Tavano, Ste","orcid":"0000-0001-9970-7804","id":"2F162F0C-F248-11E8-B48F-1D18A9856A87","last_name":"Tavano"},{"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"}],"doi":"10.1038/s41556-019-0369-3","article_processing_charge":"No","publication":"Nature Cell Biology","intvolume":"        21","isi":1,"publication_status":"published","date_published":"2019-08-01T00:00:00Z","publisher":"Springer Nature","citation":{"ama":"Tavano S, Heisenberg C-PJ. Migrasomes take center stage. <i>Nature Cell Biology</i>. 2019;21(8):918-920. doi:<a href=\"https://doi.org/10.1038/s41556-019-0369-3\">10.1038/s41556-019-0369-3</a>","chicago":"Tavano, Ste, and Carl-Philipp J Heisenberg. “Migrasomes Take Center Stage.” <i>Nature Cell Biology</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41556-019-0369-3\">https://doi.org/10.1038/s41556-019-0369-3</a>.","ista":"Tavano S, Heisenberg C-PJ. 2019. Migrasomes take center stage. Nature Cell Biology. 21(8), 918–920.","short":"S. Tavano, C.-P.J. Heisenberg, Nature Cell Biology 21 (2019) 918–920.","ieee":"S. Tavano and C.-P. J. Heisenberg, “Migrasomes take center stage,” <i>Nature Cell Biology</i>, vol. 21, no. 8. Springer Nature, pp. 918–920, 2019.","mla":"Tavano, Ste, and Carl-Philipp J. Heisenberg. “Migrasomes Take Center Stage.” <i>Nature Cell Biology</i>, vol. 21, no. 8, Springer Nature, 2019, pp. 918–20, doi:<a href=\"https://doi.org/10.1038/s41556-019-0369-3\">10.1038/s41556-019-0369-3</a>.","apa":"Tavano, S., &#38; Heisenberg, C.-P. J. (2019). Migrasomes take center stage. <i>Nature Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41556-019-0369-3\">https://doi.org/10.1038/s41556-019-0369-3</a>"},"department":[{"_id":"CaHe"}],"oa_version":"None","publication_identifier":{"eissn":["1476-4679"]}},{"issue":"11","month":"11","type":"journal_article","_id":"7105","date_updated":"2023-09-06T11:08:52Z","volume":21,"quality_controlled":"1","title":"Persistent and polarized global actin flow is essential for directionality during cell migration","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","external_id":{"pmid":["31685997"],"isi":["000495888300009"]},"scopus_import":"1","day":"01","year":"2019","status":"public","page":"1370-1381","abstract":[{"text":"Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence.","lang":"eng"}],"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025891","open_access":"1"}],"date_published":"2019-11-01T00:00:00Z","citation":{"chicago":"Yolland, Lawrence, Mubarik Burki, Stefania Marcotti, Andrei Luchici, Fiona N. Kenny, John Robert Davis, Eduardo Serna-Morales, et al. “Persistent and Polarized Global Actin Flow Is Essential for Directionality during Cell Migration.” <i>Nature Cell Biology</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41556-019-0411-5\">https://doi.org/10.1038/s41556-019-0411-5</a>.","ista":"Yolland L, Burki M, Marcotti S, Luchici A, Kenny FN, Davis JR, Serna-Morales E, Müller J, Sixt MK, Davidson A, Wood W, Schumacher LJ, Endres RG, Miodownik M, Stramer BM. 2019. Persistent and polarized global actin flow is essential for directionality during cell migration. Nature Cell Biology. 21(11), 1370–1381.","short":"L. Yolland, M. Burki, S. Marcotti, A. Luchici, F.N. Kenny, J.R. Davis, E. Serna-Morales, J. Müller, M.K. Sixt, A. Davidson, W. Wood, L.J. Schumacher, R.G. Endres, M. Miodownik, B.M. Stramer, Nature Cell Biology 21 (2019) 1370–1381.","ama":"Yolland L, Burki M, Marcotti S, et al. Persistent and polarized global actin flow is essential for directionality during cell migration. <i>Nature Cell Biology</i>. 2019;21(11):1370-1381. doi:<a href=\"https://doi.org/10.1038/s41556-019-0411-5\">10.1038/s41556-019-0411-5</a>","apa":"Yolland, L., Burki, M., Marcotti, S., Luchici, A., Kenny, F. N., Davis, J. R., … Stramer, B. M. (2019). Persistent and polarized global actin flow is essential for directionality during cell migration. <i>Nature Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41556-019-0411-5\">https://doi.org/10.1038/s41556-019-0411-5</a>","mla":"Yolland, Lawrence, et al. “Persistent and Polarized Global Actin Flow Is Essential for Directionality during Cell Migration.” <i>Nature Cell Biology</i>, vol. 21, no. 11, Springer Nature, 2019, pp. 1370–81, doi:<a href=\"https://doi.org/10.1038/s41556-019-0411-5\">10.1038/s41556-019-0411-5</a>.","ieee":"L. Yolland <i>et al.</i>, “Persistent and polarized global actin flow is essential for directionality during cell migration,” <i>Nature Cell Biology</i>, vol. 21, no. 11. Springer Nature, pp. 1370–1381, 2019."},"publisher":"Springer Nature","oa":1,"department":[{"_id":"MiSi"}],"oa_version":"Submitted Version","publication_identifier":{"issn":["1465-7392"],"eissn":["1476-4679"]},"date_created":"2019-11-25T08:55:00Z","pmid":1,"language":[{"iso":"eng"}],"author":[{"first_name":"Lawrence","last_name":"Yolland","full_name":"Yolland, Lawrence"},{"first_name":"Mubarik","full_name":"Burki, Mubarik","last_name":"Burki"},{"first_name":"Stefania","full_name":"Marcotti, Stefania","last_name":"Marcotti"},{"first_name":"Andrei","last_name":"Luchici","full_name":"Luchici, Andrei"},{"full_name":"Kenny, Fiona N.","last_name":"Kenny","first_name":"Fiona N."},{"first_name":"John Robert","full_name":"Davis, John Robert","last_name":"Davis"},{"full_name":"Serna-Morales, Eduardo","last_name":"Serna-Morales","first_name":"Eduardo"},{"first_name":"Jan","last_name":"Müller","id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D","full_name":"Müller, Jan"},{"last_name":"Sixt","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","first_name":"Michael K"},{"last_name":"Davidson","full_name":"Davidson, Andrew","first_name":"Andrew"},{"full_name":"Wood, Will","last_name":"Wood","first_name":"Will"},{"last_name":"Schumacher","full_name":"Schumacher, Linus J.","first_name":"Linus J."},{"first_name":"Robert G.","full_name":"Endres, Robert G.","last_name":"Endres"},{"first_name":"Mark","full_name":"Miodownik, Mark","last_name":"Miodownik"},{"full_name":"Stramer, Brian M.","last_name":"Stramer","first_name":"Brian M."}],"publication":"Nature Cell Biology","doi":"10.1038/s41556-019-0411-5","article_processing_charge":"No","intvolume":"        21","isi":1,"publication_status":"published","article_type":"original"},{"volume":10,"date_updated":"2026-05-29T07:13:59Z","extern":"1","issue":"4","month":"03","type":"journal_article","_id":"4181","page":"429 - 436","abstract":[{"text":"Understanding the factors that direct tissue organization during development is one of the most fundamental goals in developmental biology. Various hypotheses explain cell sorting and tissue organization on the basis of the adhesive and mechanical properties of the constituent cells(1). However, validating these hypotheses has been difficult due to the lack of appropriate tools to measure these parameters. Here we use atomic force microscopy ( AFM) to quantify the adhesive and mechanical properties of individual ectoderm, mesoderm and endoderm progenitor cells from gastrulating zebrafish embryos. Combining these data with tissue self-assembly in vitro and the sorting behaviour of progenitors in vivo, we have shown that differential actomyosin-dependent cell-cortex tension, regulated by Nodal/ TGF beta-signalling ( transforming growth factor beta), constitutes a key factor that directs progenitor-cell sorting. These results demonstrate a previously unrecognized role for Nodal-controlled cell-cortex tension in germ-layer organization during gastrulation.","lang":"eng"}],"external_id":{"pmid":["18364700 "]},"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","title":"Tensile forces govern germ-layer organization in zebrafish","day":"23","year":"2008","status":"public","oa_version":"None","OA_type":"closed access","publication_identifier":{"eissn":["1476-4679"],"issn":["1465-7392"]},"date_published":"2008-03-23T00:00:00Z","citation":{"mla":"Krieg, Michael, et al. “Tensile Forces Govern Germ-Layer Organization in Zebrafish.” <i>Nature Cell Biology</i>, vol. 10, no. 4, Nature Publishing Group, 2008, pp. 429–36, doi:<a href=\"https://doi.org/10.1038/ncb1705\">10.1038/ncb1705</a>.","apa":"Krieg, M., Arboleda Estudillo, Y., Puech, P., Käfer, J., Graner, F., Mueller, D., &#38; Heisenberg, C.-P. J. (2008). Tensile forces govern germ-layer organization in zebrafish. <i>Nature Cell Biology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/ncb1705\">https://doi.org/10.1038/ncb1705</a>","ieee":"M. Krieg <i>et al.</i>, “Tensile forces govern germ-layer organization in zebrafish,” <i>Nature Cell Biology</i>, vol. 10, no. 4. Nature Publishing Group, pp. 429–436, 2008.","chicago":"Krieg, Michael, Yohanna Arboleda Estudillo, Pierre Puech, Jos Käfer, François Graner, Daniel Mueller, and Carl-Philipp J Heisenberg. “Tensile Forces Govern Germ-Layer Organization in Zebrafish.” <i>Nature Cell Biology</i>. Nature Publishing Group, 2008. <a href=\"https://doi.org/10.1038/ncb1705\">https://doi.org/10.1038/ncb1705</a>.","ista":"Krieg M, Arboleda Estudillo Y, Puech P, Käfer J, Graner F, Mueller D, Heisenberg C-PJ. 2008. Tensile forces govern germ-layer organization in zebrafish. Nature Cell Biology. 10(4), 429–436.","short":"M. Krieg, Y. Arboleda Estudillo, P. Puech, J. Käfer, F. Graner, D. Mueller, C.-P.J. Heisenberg, Nature Cell Biology 10 (2008) 429–436.","ama":"Krieg M, Arboleda Estudillo Y, Puech P, et al. Tensile forces govern germ-layer organization in zebrafish. <i>Nature Cell Biology</i>. 2008;10(4):429-436. doi:<a href=\"https://doi.org/10.1038/ncb1705\">10.1038/ncb1705</a>"},"publisher":"Nature Publishing Group","publication":"Nature Cell Biology","doi":"10.1038/ncb1705","article_processing_charge":"No","intvolume":"        10","publication_status":"published","article_type":"letter_note","date_created":"2018-12-11T12:07:26Z","pmid":1,"language":[{"iso":"eng"}],"author":[{"first_name":"Michael","full_name":"Krieg, Michael","last_name":"Krieg"},{"last_name":"Arboleda Estudillo","full_name":"Arboleda Estudillo, Yohanna","first_name":"Yohanna"},{"last_name":"Puech","full_name":"Puech, Pierre","first_name":"Pierre"},{"first_name":"Jos","full_name":"Käfer, Jos","last_name":"Käfer"},{"first_name":"François","last_name":"Graner","full_name":"Graner, François"},{"first_name":"Daniel","full_name":"Mueller, Daniel","last_name":"Mueller"},{"full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J"}],"publist_id":"1938"},{"status":"public","day":"09","year":"2007","scopus_import":"1","external_id":{"pmid":["17828249"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum","abstract":[{"lang":"eng","text":"The formation of the nuclear envelope (NE) around chromatin is a major membrane-remodelling event that occurs during cell division of metazoa. It is unclear whether the nuclear membrane reforms by the fusion of NE fragments or if it re-emerges from an intact tubular network of the endoplasmic reticulum (ER). Here, we show that NE formation and expansion requires a tubular ER network and occurs efficiently in the presence of the membrane fusion inhibitor GTPγS. Chromatin recruitment of membranes, which is initiated by tubule-end binding, followed by the formation, expansion and sealing of flat membrane sheets, is mediated by DNA-binding proteins residing in the ER. Thus, chromatin plays an active role in reshaping of the ER during NE formation."}],"page":"1160-1166","_id":"11115","type":"journal_article","extern":"1","issue":"10","month":"09","quality_controlled":"1","volume":9,"date_updated":"2024-10-14T11:30:08Z","author":[{"first_name":"Daniel J.","full_name":"Anderson, Daniel J.","last_name":"Anderson"},{"full_name":"HETZER, Martin W","orcid":"0000-0002-2111-992X","last_name":"HETZER","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W"}],"language":[{"iso":"eng"}],"pmid":1,"date_created":"2022-04-07T07:56:04Z","keyword":["Cell Biology"],"publication_status":"published","article_type":"original","intvolume":"         9","publication":"Nature Cell Biology","article_processing_charge":"No","doi":"10.1038/ncb1636","citation":{"ista":"Anderson DJ, Hetzer M. 2007. Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum. Nature Cell Biology. 9(10), 1160–1166.","short":"D.J. Anderson, M. Hetzer, Nature Cell Biology 9 (2007) 1160–1166.","chicago":"Anderson, Daniel J., and Martin Hetzer. “Nuclear Envelope Formation by Chromatin-Mediated Reorganization of the Endoplasmic Reticulum.” <i>Nature Cell Biology</i>. Springer Nature, 2007. <a href=\"https://doi.org/10.1038/ncb1636\">https://doi.org/10.1038/ncb1636</a>.","ama":"Anderson DJ, Hetzer M. Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum. <i>Nature Cell Biology</i>. 2007;9(10):1160-1166. doi:<a href=\"https://doi.org/10.1038/ncb1636\">10.1038/ncb1636</a>","apa":"Anderson, D. J., &#38; Hetzer, M. (2007). Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum. <i>Nature Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/ncb1636\">https://doi.org/10.1038/ncb1636</a>","mla":"Anderson, Daniel J., and Martin Hetzer. “Nuclear Envelope Formation by Chromatin-Mediated Reorganization of the Endoplasmic Reticulum.” <i>Nature Cell Biology</i>, vol. 9, no. 10, Springer Nature, 2007, pp. 1160–66, doi:<a href=\"https://doi.org/10.1038/ncb1636\">10.1038/ncb1636</a>.","ieee":"D. J. Anderson and M. Hetzer, “Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum,” <i>Nature Cell Biology</i>, vol. 9, no. 10. Springer Nature, pp. 1160–1166, 2007."},"publisher":"Springer Nature","date_published":"2007-09-09T00:00:00Z","publication_identifier":{"issn":["1465-7392"],"eissn":["1476-4679"]},"oa_version":"None"},{"date_created":"2018-12-11T12:01:41Z","pmid":1,"publist_id":"3544","author":[{"full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","last_name":"Siekhaus","first_name":"Daria E"},{"first_name":"David","full_name":"Drubin, David","last_name":"Drubin"}],"language":[{"iso":"eng"}],"article_processing_charge":"No","doi":"10.1038/ncb941","publication":"Nature Cell Biology","intvolume":"         5","article_type":"letter_note","publication_status":"published","date_published":"2003-03-01T00:00:00Z","publisher":"Springer Nature","citation":{"ama":"Siekhaus DE, Drubin D. Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant. <i>Nature Cell Biology</i>. 2003;5(3):231-235. doi:<a href=\"https://doi.org/10.1038/ncb941\">10.1038/ncb941</a>","chicago":"Siekhaus, Daria E, and David Drubin. “Spontaneous Receptor-Independent Heterotrimeric G-Protein Signalling in an RGS Mutant.” <i>Nature Cell Biology</i>. Springer Nature, 2003. <a href=\"https://doi.org/10.1038/ncb941\">https://doi.org/10.1038/ncb941</a>.","short":"D.E. Siekhaus, D. Drubin, Nature Cell Biology 5 (2003) 231–235.","ista":"Siekhaus DE, Drubin D. 2003. Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant. Nature Cell Biology. 5(3), 231–235.","ieee":"D. E. Siekhaus and D. Drubin, “Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant,” <i>Nature Cell Biology</i>, vol. 5, no. 3. Springer Nature, pp. 231–235, 2003.","apa":"Siekhaus, D. E., &#38; Drubin, D. (2003). Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant. <i>Nature Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/ncb941\">https://doi.org/10.1038/ncb941</a>","mla":"Siekhaus, Daria E., and David Drubin. “Spontaneous Receptor-Independent Heterotrimeric G-Protein Signalling in an RGS Mutant.” <i>Nature Cell Biology</i>, vol. 5, no. 3, Springer Nature, 2003, pp. 231–35, doi:<a href=\"https://doi.org/10.1038/ncb941\">10.1038/ncb941</a>."},"oa_version":"None","publication_identifier":{"eissn":["1476-4679"],"issn":["1465-7392"]},"OA_type":"closed access","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","external_id":{"pmid":["12598904 "]},"title":"Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant","year":"2003","day":"01","status":"public","page":"231 - 235","abstract":[{"lang":"eng","text":"Tripartite G-protein-coupled receptors (GPCRs) represent one of the largest groups of signal transducers, transmitting signals from hormones, neuropeptides, odorants, food and light. Ligand-bound receptors catalyse GDP/GTP exchange on the G-protein α-subunit (Gα), leading to α-GTP separation from the βγ subunits and pathway activation. Activating mutations in the receptors or G proteins underlie many human diseases, including some cancers, dwarfism and premature puberty. Regulators of G-protein signalling (RGS proteins) are known to modulate the level and duration of ligand-induced signalling by accelerating the intrinsic GTPase activity of the Gα subunit, and thus reformation of the inactive GDP-bound Gα. Here we find that even in the absence of receptor, mutation of the RGS family member Sst2 (refs 6-9) permits spontaneous activation of the G-protein-coupled mating pathway in Saccharomyces cerevisiae at levels normally seen only in the presence of ligand. Our work demonstrates the occurence of spontaneous tripartite G-protein signalling in vivo and identifies a requirement for RGS proteins in preventing such receptor-independent activation."}],"month":"03","extern":"1","issue":"3","type":"journal_article","_id":"3150","volume":5,"date_updated":"2026-05-21T13:51:51Z","quality_controlled":"1"},{"external_id":{"pmid":["12105431"]},"title":"The Ran GTPase as a marker of chromosome position in spindle formation and nuclear envelope assembly","user_id":"72615eeb-f1f3-11ec-aa25-d4573ddc34fd","scopus_import":"1","year":"2002","day":"01","status":"public","page":"E177-E184","abstract":[{"lang":"eng","text":"The small GTPase Ran is a key regulator of nucleocytoplasmic transport during interphase. The asymmetric distribution of the GTP-bound form of Ran across the nuclear envelope — that is, large quantities in the nucleus compared with small quantities in the cytoplasm — determines the directionality of many nuclear transport processes. Recent findings that Ran also functions in spindle formation and nuclear envelope assembly during mitosis suggest that Ran has a general role in chromatin-centred processes. Ran functions in these events as a signal for chromosome position."}],"month":"07","issue":"7","extern":"1","type":"journal_article","_id":"11123","volume":4,"date_updated":"2022-07-18T08:58:03Z","quality_controlled":"1","keyword":["Cell Biology"],"date_created":"2022-04-07T07:57:19Z","pmid":1,"author":[{"first_name":"Martin W","full_name":"HETZER, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","orcid":"0000-0002-2111-992X","last_name":"HETZER"},{"last_name":"Gruss","full_name":"Gruss, Oliver J.","first_name":"Oliver J."},{"full_name":"Mattaj, Iain W.","last_name":"Mattaj","first_name":"Iain W."}],"language":[{"iso":"eng"}],"doi":"10.1038/ncb0702-e177","article_processing_charge":"No","publication":"Nature Cell Biology","intvolume":"         4","article_type":"original","publication_status":"published","date_published":"2002-07-01T00:00:00Z","publisher":"Springer Nature","citation":{"ieee":"M. Hetzer, O. J. Gruss, and I. W. Mattaj, “The Ran GTPase as a marker of chromosome position in spindle formation and nuclear envelope assembly,” <i>Nature Cell Biology</i>, vol. 4, no. 7. Springer Nature, pp. E177–E184, 2002.","mla":"Hetzer, Martin, et al. “The Ran GTPase as a Marker of Chromosome Position in Spindle Formation and Nuclear Envelope Assembly.” <i>Nature Cell Biology</i>, vol. 4, no. 7, Springer Nature, 2002, pp. E177–84, doi:<a href=\"https://doi.org/10.1038/ncb0702-e177\">10.1038/ncb0702-e177</a>.","apa":"Hetzer, M., Gruss, O. J., &#38; Mattaj, I. W. (2002). The Ran GTPase as a marker of chromosome position in spindle formation and nuclear envelope assembly. <i>Nature Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/ncb0702-e177\">https://doi.org/10.1038/ncb0702-e177</a>","ama":"Hetzer M, Gruss OJ, Mattaj IW. The Ran GTPase as a marker of chromosome position in spindle formation and nuclear envelope assembly. <i>Nature Cell Biology</i>. 2002;4(7):E177-E184. doi:<a href=\"https://doi.org/10.1038/ncb0702-e177\">10.1038/ncb0702-e177</a>","chicago":"Hetzer, Martin, Oliver J. Gruss, and Iain W. Mattaj. “The Ran GTPase as a Marker of Chromosome Position in Spindle Formation and Nuclear Envelope Assembly.” <i>Nature Cell Biology</i>. Springer Nature, 2002. <a href=\"https://doi.org/10.1038/ncb0702-e177\">https://doi.org/10.1038/ncb0702-e177</a>.","short":"M. Hetzer, O.J. Gruss, I.W. Mattaj, Nature Cell Biology 4 (2002) E177–E184.","ista":"Hetzer M, Gruss OJ, Mattaj IW. 2002. The Ran GTPase as a marker of chromosome position in spindle formation and nuclear envelope assembly. Nature Cell Biology. 4(7), E177–E184."},"oa_version":"None","publication_identifier":{"eissn":["1476-4679"],"issn":["1465-7392"]}},{"day":"02","year":"2001","status":"public","title":"Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly","user_id":"72615eeb-f1f3-11ec-aa25-d4573ddc34fd","external_id":{"pmid":["11781570"]},"scopus_import":"1","page":"1086-1091","abstract":[{"lang":"eng","text":"Although nuclear envelope (NE) assembly is known to require the GTPase Ran, the membrane fusion machinery involved is uncharacterized. NE assembly involves formation of a reticular network on chromatin, fusion of this network into a closed NE and subsequent expansion. Here we show that p97, an AAA-ATPase previously implicated in fusion of Golgi and transitional endoplasmic reticulum (ER) membranes together with the adaptor p47, has two discrete functions in NE assembly. Formation of a closed NE requires the p97–Ufd1–Npl4 complex, not previously implicated in membrane fusion. Subsequent NE growth involves a p97–p47 complex. This study provides the first insights into the molecular mechanisms and specificity of fusion events involved in NE formation."}],"_id":"11125","extern":"1","issue":"12","month":"11","type":"journal_article","quality_controlled":"1","volume":3,"date_updated":"2022-07-18T08:58:07Z","pmid":1,"language":[{"iso":"eng"}],"author":[{"first_name":"Martin W","full_name":"HETZER, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","orcid":"0000-0002-2111-992X","last_name":"HETZER"},{"last_name":"Meyer","full_name":"Meyer, Hemmo H.","first_name":"Hemmo H."},{"first_name":"Tobias C.","last_name":"Walther","full_name":"Walther, Tobias C."},{"first_name":"Daniel","full_name":"Bilbao-Cortes, Daniel","last_name":"Bilbao-Cortes"},{"last_name":"Warren","full_name":"Warren, Graham","first_name":"Graham"},{"first_name":"Iain W.","last_name":"Mattaj","full_name":"Mattaj, Iain W."}],"date_created":"2022-04-07T07:57:42Z","keyword":["Cell Biology"],"intvolume":"         3","publication_status":"published","article_type":"original","publication":"Nature Cell Biology","article_processing_charge":"No","doi":"10.1038/ncb1201-1086","citation":{"ama":"Hetzer M, Meyer HH, Walther TC, Bilbao-Cortes D, Warren G, Mattaj IW. Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly. <i>Nature Cell Biology</i>. 2001;3(12):1086-1091. doi:<a href=\"https://doi.org/10.1038/ncb1201-1086\">10.1038/ncb1201-1086</a>","ista":"Hetzer M, Meyer HH, Walther TC, Bilbao-Cortes D, Warren G, Mattaj IW. 2001. Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly. Nature Cell Biology. 3(12), 1086–1091.","chicago":"Hetzer, Martin, Hemmo H. Meyer, Tobias C. Walther, Daniel Bilbao-Cortes, Graham Warren, and Iain W. Mattaj. “Distinct AAA-ATPase P97 Complexes Function in Discrete Steps of Nuclear Assembly.” <i>Nature Cell Biology</i>. Springer Nature, 2001. <a href=\"https://doi.org/10.1038/ncb1201-1086\">https://doi.org/10.1038/ncb1201-1086</a>.","short":"M. Hetzer, H.H. Meyer, T.C. Walther, D. Bilbao-Cortes, G. Warren, I.W. Mattaj, Nature Cell Biology 3 (2001) 1086–1091.","ieee":"M. Hetzer, H. H. Meyer, T. C. Walther, D. Bilbao-Cortes, G. Warren, and I. W. Mattaj, “Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly,” <i>Nature Cell Biology</i>, vol. 3, no. 12. Springer Nature, pp. 1086–1091, 2001.","apa":"Hetzer, M., Meyer, H. H., Walther, T. C., Bilbao-Cortes, D., Warren, G., &#38; Mattaj, I. W. (2001). Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly. <i>Nature Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/ncb1201-1086\">https://doi.org/10.1038/ncb1201-1086</a>","mla":"Hetzer, Martin, et al. “Distinct AAA-ATPase P97 Complexes Function in Discrete Steps of Nuclear Assembly.” <i>Nature Cell Biology</i>, vol. 3, no. 12, Springer Nature, 2001, pp. 1086–91, doi:<a href=\"https://doi.org/10.1038/ncb1201-1086\">10.1038/ncb1201-1086</a>."},"publisher":"Springer Nature","date_published":"2001-11-02T00:00:00Z","oa_version":"None","publication_identifier":{"eissn":["1476-4679"],"issn":["1465-7392"]}}]