[{"status":"public","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"volume":"179-180","article_processing_charge":"Yes (in subscription journal)","quality_controlled":"1","article_type":"review","file_date_updated":"2026-04-28T13:58:47Z","abstract":[{"text":"Epithelial tissues function as multicellular communities that preserve tissue integrity while adapting to diverse environmental stresses by altering cell behaviors. A striking manifestation of such adaptability is cell plasticity, the ability of differentiated cells to revert to stem-like states or adopt alternative fates. Once considered rare and confined to highly regenerative species, cell plasticity is now recognized across the metazoan tree. In early-branching animals such as sponges and cnidarians, transdifferentiation and dedifferentiation are integral to life-cycle transitions and regeneration, whereas in more complex organisms, these processes typically emerge under stress, including stem cell loss or environmental perturbations. Here, we examine epithelial cell plasticity through evolutionary, cellular, and molecular perspectives. Focusing on the intestinal epithelium, we explore findings from mammalian and Drosophila models showing that progenitors and even terminally differentiated cells can dedifferentiate in response to external stimuli that disrupt homeostasis, such as pathogen infection and nutrient fluctuations. We further discuss conserved mechanisms involving intercellular signaling (e.g., Notch, EGFR, and JAK-STAT) and chromatin states primed for reprogramming, modulated by metabolic cues. Together, these insights position cell plasticity as an ancient environmental adaptation strategy, shaped by conserved molecular toolkits and refined by species- and cell lineage-specific innovations.","lang":"eng"}],"language":[{"iso":"eng"}],"license":"https://creativecommons.org/licenses/by/4.0/","oa_version":"Published Version","OA_place":"publisher","article_number":"103670","date_published":"2026-05-01T00:00:00Z","acknowledgement":"This work was supported by JSPS/MEXT KAKENHI (grant numbers JP22J01430 to H.N., JP23H04696, JP23K24025, JP25H02543, JP25K02406 to Y.N.), JST FOREST Program JPMJFR233E (Y.N.), The Cell Science Research Foundation (Y.N.), and Takeda Science Foundation (Y.N.).","has_accepted_license":"1","scopus_import":"1","department":[{"_id":"XiFe"}],"publication_status":"published","file":[{"date_created":"2026-04-28T13:58:47Z","access_level":"open_access","file_size":1306613,"relation":"main_file","checksum":"0a0929a045d0cbd964297768833c14ae","content_type":"application/pdf","creator":"dernst","success":1,"file_id":"21775","file_name":"2026_SeminarsCellDevBiology_Nagai.pdf","date_updated":"2026-04-28T13:58:47Z"}],"_id":"21752","day":"01","OA_type":"hybrid","oa":1,"ddc":["570"],"date_created":"2026-04-19T22:07:49Z","publisher":"Elsevier","date_updated":"2026-04-28T14:11:13Z","year":"2026","corr_author":"1","publication":"Seminars in Cell and Developmental Biology","publication_identifier":{"eissn":["1096-3634"],"issn":["1084-9521"]},"PlanS_conform":"1","title":"Epithelial cell plasticity in metazoans: Evolutionary insights into roles and mechanisms","citation":{"ama":"NAGAI H, Nakajima YI. Epithelial cell plasticity in metazoans: Evolutionary insights into roles and mechanisms. <i>Seminars in Cell and Developmental Biology</i>. 2026;179-180. doi:<a href=\"https://doi.org/10.1016/j.semcdb.2026.103670\">10.1016/j.semcdb.2026.103670</a>","chicago":"NAGAI, HIROKI, and Yu Ichiro Nakajima. “Epithelial Cell Plasticity in Metazoans: Evolutionary Insights into Roles and Mechanisms.” <i>Seminars in Cell and Developmental Biology</i>. Elsevier, 2026. <a href=\"https://doi.org/10.1016/j.semcdb.2026.103670\">https://doi.org/10.1016/j.semcdb.2026.103670</a>.","ista":"NAGAI H, Nakajima YI. 2026. Epithelial cell plasticity in metazoans: Evolutionary insights into roles and mechanisms. Seminars in Cell and Developmental Biology. 179–180, 103670.","apa":"NAGAI, H., &#38; Nakajima, Y. I. (2026). Epithelial cell plasticity in metazoans: Evolutionary insights into roles and mechanisms. <i>Seminars in Cell and Developmental Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.semcdb.2026.103670\">https://doi.org/10.1016/j.semcdb.2026.103670</a>","short":"H. NAGAI, Y.I. Nakajima, Seminars in Cell and Developmental Biology 179–180 (2026).","mla":"NAGAI, HIROKI, and Yu Ichiro Nakajima. “Epithelial Cell Plasticity in Metazoans: Evolutionary Insights into Roles and Mechanisms.” <i>Seminars in Cell and Developmental Biology</i>, vol. 179–180, 103670, Elsevier, 2026, doi:<a href=\"https://doi.org/10.1016/j.semcdb.2026.103670\">10.1016/j.semcdb.2026.103670</a>.","ieee":"H. NAGAI and Y. I. Nakajima, “Epithelial cell plasticity in metazoans: Evolutionary insights into roles and mechanisms,” <i>Seminars in Cell and Developmental Biology</i>, vol. 179–180. Elsevier, 2026."},"doi":"10.1016/j.semcdb.2026.103670","author":[{"first_name":"Hiroki","orcid":"0000-0003-1671-9434","last_name":"Nagai","id":"608df3e6-e2ab-11ed-8890-c9318cec7da4","full_name":"Nagai, Hiroki"},{"last_name":"Nakajima","full_name":"Nakajima, Yu Ichiro","first_name":"Yu Ichiro"}],"month":"05","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"scopus_import":"1","department":[{"_id":"CaHe"}],"isi":1,"article_number":"103650","date_published":"2025-12-01T00:00:00Z","acknowledgement":"We thank Carolina Camelo for making schematics for this review.","has_accepted_license":"1","OA_place":"publisher","pmid":1,"file_date_updated":"2025-12-30T10:21:00Z","abstract":[{"lang":"eng","text":"Oogenesis – the formation and development of an oocyte – is fundamental to reproduction and embryonic development. Due to its accessibility to genetic manipulations and the ability to culture and experimentally manipulate oocytes ex vivo, zebrafish has emerged as a powerful vertebrate model system for studying oogenesis. In this review, we provide a comprehensive overview of zebrafish oogenesis, from early germ cell formation to oocyte maturation and fertilization. We discuss recent advances in uncovering the molecular and cellular mechanisms driving this complex process and highlight key knowledge gaps that remain to be addressed."}],"language":[{"iso":"eng"}],"oa_version":"Published Version","article_processing_charge":"Yes (via OA deal)","quality_controlled":"1","article_type":"review","intvolume":"       175","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"volume":175,"type":"journal_article","status":"public","doi":"10.1016/j.semcdb.2025.103650","author":[{"id":"b88d43f2-dc74-11ea-a0a7-e41b7912e031","full_name":"Hofmann, Laura","last_name":"Hofmann","first_name":"Laura"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"12","external_id":{"pmid":["40913907"],"isi":["001567260100001"]},"citation":{"ama":"Hofmann L, Heisenberg C-PJ. Decoding zebrafish oogenesis: From primordial germ cell development to fertilization. <i>Seminars in Cell and Developmental Biology</i>. 2025;175. doi:<a href=\"https://doi.org/10.1016/j.semcdb.2025.103650\">10.1016/j.semcdb.2025.103650</a>","chicago":"Hofmann, Laura, and Carl-Philipp J Heisenberg. “Decoding Zebrafish Oogenesis: From Primordial Germ Cell Development to Fertilization.” <i>Seminars in Cell and Developmental Biology</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.semcdb.2025.103650\">https://doi.org/10.1016/j.semcdb.2025.103650</a>.","ista":"Hofmann L, Heisenberg C-PJ. 2025. Decoding zebrafish oogenesis: From primordial germ cell development to fertilization. Seminars in Cell and Developmental Biology. 175, 103650.","apa":"Hofmann, L., &#38; Heisenberg, C.-P. J. (2025). Decoding zebrafish oogenesis: From primordial germ cell development to fertilization. <i>Seminars in Cell and Developmental Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.semcdb.2025.103650\">https://doi.org/10.1016/j.semcdb.2025.103650</a>","short":"L. Hofmann, C.-P.J. Heisenberg, Seminars in Cell and Developmental Biology 175 (2025).","mla":"Hofmann, Laura, and Carl-Philipp J. Heisenberg. “Decoding Zebrafish Oogenesis: From Primordial Germ Cell Development to Fertilization.” <i>Seminars in Cell and Developmental Biology</i>, vol. 175, 103650, Elsevier, 2025, doi:<a href=\"https://doi.org/10.1016/j.semcdb.2025.103650\">10.1016/j.semcdb.2025.103650</a>.","ieee":"L. Hofmann and C.-P. J. Heisenberg, “Decoding zebrafish oogenesis: From primordial germ cell development to fertilization,” <i>Seminars in Cell and Developmental Biology</i>, vol. 175. Elsevier, 2025."},"publication_identifier":{"eissn":["1096-3634"],"issn":["1084-9521"]},"title":"Decoding zebrafish oogenesis: From primordial germ cell development to fertilization","PlanS_conform":"1","publisher":"Elsevier","date_updated":"2025-12-30T10:21:13Z","corr_author":"1","year":"2025","publication":"Seminars in Cell and Developmental Biology","oa":1,"ddc":["570"],"date_created":"2025-09-14T22:01:32Z","_id":"20349","day":"01","OA_type":"hybrid","publication_status":"published","file":[{"content_type":"application/pdf","checksum":"80ea6cbb004853bb1e87db3422a74aca","creator":"dernst","file_size":2778561,"relation":"main_file","access_level":"open_access","date_created":"2025-12-30T10:21:00Z","date_updated":"2025-12-30T10:21:00Z","file_name":"2025_SemCellDevBiology_Hofmann.pdf","file_id":"20914","success":1}]},{"ec_funded":1,"_id":"12162","day":"02","ddc":["570"],"date_created":"2023-01-12T12:09:47Z","oa":1,"keyword":["Cell Biology","Developmental Biology"],"file":[{"content_type":"application/pdf","checksum":"c619887cf130f4649bf3035417186004","creator":"dernst","file_size":1343750,"relation":"main_file","access_level":"open_access","date_created":"2024-01-08T10:16:04Z","date_updated":"2024-01-08T10:16:04Z","file_name":"2023_SeminarsCellDevBiology_CorominasMurtra.pdf","file_id":"14741","success":1}],"publication_status":"published","external_id":{"isi":["001053522200001"],"pmid":["36470715"]},"citation":{"ama":"Corominas-Murtra B, Hannezo EB. Modelling the dynamics of mammalian gut homeostasis. <i>Seminars in Cell &#38; Developmental Biology</i>. 2023;150-151:58-65. doi:<a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">10.1016/j.semcdb.2022.11.005</a>","chicago":"Corominas-Murtra, Bernat, and Edouard B Hannezo. “Modelling the Dynamics of Mammalian Gut Homeostasis.” <i>Seminars in Cell &#38; Developmental Biology</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">https://doi.org/10.1016/j.semcdb.2022.11.005</a>.","ista":"Corominas-Murtra B, Hannezo EB. 2023. Modelling the dynamics of mammalian gut homeostasis. Seminars in Cell &#38; Developmental Biology. 150–151, 58–65.","short":"B. Corominas-Murtra, E.B. Hannezo, Seminars in Cell &#38; Developmental Biology 150–151 (2023) 58–65.","apa":"Corominas-Murtra, B., &#38; Hannezo, E. B. (2023). Modelling the dynamics of mammalian gut homeostasis. <i>Seminars in Cell &#38; Developmental Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">https://doi.org/10.1016/j.semcdb.2022.11.005</a>","mla":"Corominas-Murtra, Bernat, and Edouard B. Hannezo. “Modelling the Dynamics of Mammalian Gut Homeostasis.” <i>Seminars in Cell &#38; Developmental Biology</i>, vol. 150–151, Elsevier, 2023, pp. 58–65, doi:<a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">10.1016/j.semcdb.2022.11.005</a>.","ieee":"B. Corominas-Murtra and E. B. Hannezo, “Modelling the dynamics of mammalian gut homeostasis,” <i>Seminars in Cell &#38; Developmental Biology</i>, vol. 150–151. Elsevier, pp. 58–65, 2023."},"author":[{"last_name":"Corominas-Murtra","id":"43BE2298-F248-11E8-B48F-1D18A9856A87","full_name":"Corominas-Murtra, Bernat","first_name":"Bernat","orcid":"0000-0001-9806-5643"},{"orcid":"0000-0001-6005-1561","first_name":"Edouard B","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo"}],"doi":"10.1016/j.semcdb.2022.11.005","month":"12","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"Seminars in Cell & Developmental Biology","date_updated":"2025-04-14T07:52:27Z","publisher":"Elsevier","corr_author":"1","year":"2023","publication_identifier":{"issn":["1084-9521"]},"title":"Modelling the dynamics of mammalian gut homeostasis","quality_controlled":"1","article_type":"review","article_processing_charge":"Yes (via OA deal)","page":"58-65","language":[{"iso":"eng"}],"oa_version":"Published Version","file_date_updated":"2024-01-08T10:16:04Z","abstract":[{"lang":"eng","text":"Homeostatic balance in the intestinal epithelium relies on a fast cellular turnover, which is coordinated by an intricate interplay between biochemical signalling, mechanical forces and organ geometry. We review recent modelling approaches that have been developed to understand different facets of this remarkable homeostatic equilibrium. Existing models offer different, albeit complementary, perspectives on the problem. First, biomechanical models aim to explain the local and global mechanical stresses driving cell renewal as well as tissue shape maintenance. Second, compartmental models provide insights into the conditions necessary to keep a constant flow of cells with well-defined ratios of cell types, and how perturbations can lead to an unbalance of relative compartment sizes. A third family of models address, at the cellular level, the nature and regulation of stem fate choices that are necessary to fuel cellular turnover. We also review how these different approaches are starting to be integrated together across scales, to provide quantitative predictions and new conceptual frameworks to think about the dynamics of cell renewal in complex tissues."}],"type":"journal_article","status":"public","volume":"150-151","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"has_accepted_license":"1","date_published":"2023-12-02T00:00:00Z","acknowledgement":"This work received funding from the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 851288 to E.H.).\r\nB. C-M wants to acknowledge the support of the field of excellence Complexity of Life, in Basic Research and Innovation of the University of Graz.","department":[{"_id":"EdHa"}],"isi":1,"scopus_import":"1","pmid":1,"project":[{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"}]},{"pmid":1,"acknowledgement":"We would like to thank Steve Wilson for encouraging us to write this article and for critical comments on this manuscript, and Lila Solnica-Krezel for communicating results prior to publication. MT is supported by an MRC Career Development Award, MLC by a Wellcome Trust Fellowship and CPH by an Emmy–Noether–Fellowship from the DFG.","date_published":"2002-06-01T00:00:00Z","scopus_import":"1","type":"journal_article","status":"public","extern":"1","intvolume":"        13","volume":13,"article_processing_charge":"No","article_type":"original","quality_controlled":"1","abstract":[{"text":"Members of the Wnt family have been implicated in a variety of developmental processes including axis formation, Patterning of the central nervous system and tissue morphogenesis. Recent studies have shown that a Wnt signalling pathway similar to that involved in the establishment of planar cell polarity in Drosophila regulates convergent extension movements during zebrafish and Xenopus gastrulation. This finding provides a good starting point to dissect the complex cell biology and genetic regulation of vertebrate gastrulation movements.","lang":"eng"}],"oa_version":"None","language":[{"iso":"eng"}],"page":"251 - 260","year":"2002","date_updated":"2023-06-07T09:50:14Z","publisher":"Academic Press","publication":"Seminars in Cell & Developmental Biology","title":"Non-canonical Wnt signalling and regulation of gastrulation movements","publication_identifier":{"issn":["1084-9521"]},"citation":{"ama":"Tada M, Concha M, Heisenberg C-PJ. Non-canonical Wnt signalling and regulation of gastrulation movements. <i>Seminars in Cell &#38; Developmental Biology</i>. 2002;13(3):251-260. doi:<a href=\"https://doi.org/10.1016/S1084-9521(02)00052-6\">10.1016/S1084-9521(02)00052-6</a>","chicago":"Tada, Masazumi, Miguel Concha, and Carl-Philipp J Heisenberg. “Non-Canonical Wnt Signalling and Regulation of Gastrulation Movements.” <i>Seminars in Cell &#38; Developmental Biology</i>. Academic Press, 2002. <a href=\"https://doi.org/10.1016/S1084-9521(02)00052-6\">https://doi.org/10.1016/S1084-9521(02)00052-6</a>.","ista":"Tada M, Concha M, Heisenberg C-PJ. 2002. Non-canonical Wnt signalling and regulation of gastrulation movements. Seminars in Cell &#38; Developmental Biology. 13(3), 251–260.","apa":"Tada, M., Concha, M., &#38; Heisenberg, C.-P. J. (2002). Non-canonical Wnt signalling and regulation of gastrulation movements. <i>Seminars in Cell &#38; Developmental Biology</i>. Academic Press. <a href=\"https://doi.org/10.1016/S1084-9521(02)00052-6\">https://doi.org/10.1016/S1084-9521(02)00052-6</a>","short":"M. Tada, M. Concha, C.-P.J. Heisenberg, Seminars in Cell &#38; Developmental Biology 13 (2002) 251–260.","mla":"Tada, Masazumi, et al. “Non-Canonical Wnt Signalling and Regulation of Gastrulation Movements.” <i>Seminars in Cell &#38; Developmental Biology</i>, vol. 13, no. 3, Academic Press, 2002, pp. 251–60, doi:<a href=\"https://doi.org/10.1016/S1084-9521(02)00052-6\">10.1016/S1084-9521(02)00052-6</a>.","ieee":"M. Tada, M. Concha, and C.-P. J. Heisenberg, “Non-canonical Wnt signalling and regulation of gastrulation movements,” <i>Seminars in Cell &#38; Developmental Biology</i>, vol. 13, no. 3. Academic Press, pp. 251–260, 2002."},"external_id":{"pmid":["12137734"]},"user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","month":"06","publist_id":"1973","author":[{"full_name":"Tada, Masazumi","last_name":"Tada","first_name":"Masazumi"},{"first_name":"Miguel","last_name":"Concha","full_name":"Concha, Miguel"},{"first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J"}],"doi":"10.1016/S1084-9521(02)00052-6","publication_status":"published","issue":"3","day":"01","_id":"4148","date_created":"2018-12-11T12:07:13Z"},{"_id":"4196","day":"01","date_created":"2018-12-11T12:07:31Z","publication_status":"published","issue":"6","external_id":{"pmid":["12468250"]},"citation":{"ista":"Heisenberg C-PJ, Tada M. 2002. Zebrafish gastrulation movements: bridging cell and developmental biology. Seminars in Cell &#38; Developmental Biology. 13(6), 471–479.","chicago":"Heisenberg, Carl-Philipp J, and Masazumi Tada. “Zebrafish Gastrulation Movements: Bridging Cell and Developmental Biology.” <i>Seminars in Cell &#38; Developmental Biology</i>. Academic Press, 2002. <a href=\"https://doi.org/10.1016/S1084952102001003\">https://doi.org/10.1016/S1084952102001003</a>.","ama":"Heisenberg C-PJ, Tada M. Zebrafish gastrulation movements: bridging cell and developmental biology. <i>Seminars in Cell &#38; Developmental Biology</i>. 2002;13(6):471-479. doi:<a href=\"https://doi.org/10.1016/S1084952102001003\">10.1016/S1084952102001003</a>","ieee":"C.-P. J. Heisenberg and M. Tada, “Zebrafish gastrulation movements: bridging cell and developmental biology,” <i>Seminars in Cell &#38; Developmental Biology</i>, vol. 13, no. 6. Academic Press, pp. 471–479, 2002.","mla":"Heisenberg, Carl-Philipp J., and Masazumi Tada. “Zebrafish Gastrulation Movements: Bridging Cell and Developmental Biology.” <i>Seminars in Cell &#38; Developmental Biology</i>, vol. 13, no. 6, Academic Press, 2002, pp. 471–79, doi:<a href=\"https://doi.org/10.1016/S1084952102001003\">10.1016/S1084952102001003</a>.","short":"C.-P.J. Heisenberg, M. Tada, Seminars in Cell &#38; Developmental Biology 13 (2002) 471–479.","apa":"Heisenberg, C.-P. J., &#38; Tada, M. (2002). Zebrafish gastrulation movements: bridging cell and developmental biology. <i>Seminars in Cell &#38; Developmental Biology</i>. Academic Press. <a href=\"https://doi.org/10.1016/S1084952102001003\">https://doi.org/10.1016/S1084952102001003</a>"},"author":[{"id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J"},{"first_name":"Masazumi","full_name":"Tada, Masazumi","last_name":"Tada"}],"publist_id":"1920","doi":"10.1016/S1084952102001003","month":"12","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","date_updated":"2023-06-07T09:28:48Z","publisher":"Academic Press","year":"2002","publication":"Seminars in Cell & Developmental Biology","publication_identifier":{"issn":["1084-9521"]},"title":"Zebrafish gastrulation movements: bridging cell and developmental biology","article_processing_charge":"No","quality_controlled":"1","article_type":"original","abstract":[{"text":"During vertebrate gastrulation, large cellular rearrangements lead to the formation of the three germ layers, ectoderm, mesoderm and endoderm. Zebrafish offer many genetic and experimental advantages for studying vertebrate gastrulation movements. For instance, several mutants, including silberblick, knypek and trilobite, exhibit defects in morphogenesis during gastrulation. The identification of the genes mutated in these lines together with the analysis of the mutant phenotypes has provided new insights into the molecular and cellular mechanisms that underlie vertebrate gastrulation movements.","lang":"eng"}],"language":[{"iso":"eng"}],"page":"471 - 479","oa_version":"None","type":"journal_article","status":"public","extern":"1","volume":13,"intvolume":"        13","date_published":"2002-12-01T00:00:00Z","acknowledgement":"We would like to thank Miguel Concha, Will Norton, Tim Geach, Suzanne Eaton, Kimbo Kotovic, Jenny Geiger and Steve Wilson for critical comments on this manuscript, and Lila Solnica-Krezel for providing results prior to publication. C.-P.H. is supported by an Emmy-Noether-Fellowship from the DFG and M.T. by an MRC Career Development Award.","scopus_import":"1","pmid":1}]