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Transforming growth factor beta (TGF\u03b2) signalling is essential for VBW closure, but the responding cells are not known. Here, we identify in mouse a population of migratory myofibroblasts at the leading edge of the closing VBW that express the actin-binding protein transgelin (TAGLN) and TGF\u03b2 receptor (TGF\u03b2R). These cells respond to a temporally regulated TGF\u03b22 gradient originating from the epithelium of the primary body wall. Targeted elimination of TGF\u03b2R2 in TAGLN+ cells impairs midline closure and prevents the correct subsequent patterning of the musculature and skeletal components. Remarkably, deletion of Tgfbr2 in myogenic or chondrogenic progenitor cells does not manifest in midline defects. Our results indicate a pivotal significance of VBW myofibroblasts in orchestrating ventral midline closure by mediating the response to the TGF\u03b2 gradient. Altogether, our data enable us to distinguish highly regulated epithelial-mesenchymal signalling and successive cellular migration events in VBW closure that explain early morphological changes underlying the development of congenital VBW defects.<\/jats:p>","DOI":"10.1242\/dev.152843","type":"journal-article","created":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T00:20:10Z","timestamp":1502756410000},"page":"3336-3348","source":"Crossref","is-referenced-by-count":27,"title":["Transgelin-expressing myofibroblasts orchestrate ventral midline closure through TGF\u03b2 signalling"],"prefix":"10.1242","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3544-6147","authenticated-orcid":false,"given":"Bashar","family":"Aldeiri","sequence":"first","affiliation":[{"name":"Manchester Academic Health Science Centre 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"},{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"},{"name":"Royal Manchester Children's Hospital 2 , Manchester M13 9WL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7849-2055","authenticated-orcid":false,"given":"Urmas","family":"Roostalu","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Science Centre 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"},{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Albertini","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Science Centre 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"},{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2592-3226","authenticated-orcid":false,"given":"Jason","family":"Wong","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Science Centre 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"},{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"},{"name":"University Hospitals of South Manchester 3 , Manchester M23 9LT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5323-3620","authenticated-orcid":false,"given":"Antonino","family":"Morabito","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Science Centre 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"},{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"},{"name":"Royal Manchester Children's Hospital 2 , Manchester M13 9WL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-9593","authenticated-orcid":false,"given":"Giulio","family":"Cossu","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Science Centre 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"},{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester 1 , Division of Cell Matrix Biology and Regenerative Medicine , , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061215570929700_DEV152843C1","doi-asserted-by":"publisher","first-page":"37798","DOI":"10.1074\/jbc.M006323200","article-title":"Positive- and negative-acting Kr\u00fcppel-like transcription factors bind a transforming growth factor beta control element required for expression of the smooth muscle cell differentiation marker SM22alpha in vivo","volume":"275","author":"Adam","year":"2000","journal-title":"J. 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