{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T02:39:58Z","timestamp":1770431998787,"version":"3.49.0"},"reference-count":48,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-2\/"}],"funder":[{"name":"King's College London"},{"name":"Universit\u00e9 Paris"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Microtia is a common feature of several human syndromes affecting the external ear (pinna), yet the cellular and molecular mechanisms remain poorly understood. Using human embryos and mouse models of branchio-oto-renal (BOR) and 22q11.2 deletion syndromes, we show that the syndromic genes Eya1 and Tbx1 are expressed in mesoderm-derived auricular muscle. In Eya1 mutant mice, auricular muscles failed to form and pinna morphogenesis was disrupted, with comparable defects observed in mesoderm-specific Tbx1 mutants. Both mutant pinnae exhibited impaired cartilage differentiation, suggesting that auricular muscle provides signals to the neural crest\u2013derived mesenchyme to regulate cartilage differentiation. In contrast, defects in cartilage development alone or loss of muscle contraction did not affect early pinna morphogenesis. Auricular myocytes expressed Fgfs, while the surrounding mesenchyme expressed Fgfr1, Fgfr2 and ERM proteins. Disrupted Fgf signalling was observed in mutant cartilage and muscle. In ex vivo cultures, inhibition of Fgf or Bmp signalling recapitulated cartilage defects, whereas BMP4 restored Sox9 expression. These findings identify the mesoderm as essential for pinna initiation and morphogenesis, and reveal signalling mechanisms underlying microtia in BOR and 22q11.2 deletion syndromes.<\/jats:p>","DOI":"10.1242\/dev.204784","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T13:33:58Z","timestamp":1770384838000},"source":"Crossref","is-referenced-by-count":0,"title":["Analysis of\n                    <i>Eya1<\/i>\n                    and\n                    <i>Tbx1<\/i>\n                    mutants highlights interactions between the muscle and developing cartilage during external ear formation"],"prefix":"10.1242","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6044-1989","authenticated-orcid":false,"given":"Juan M.","family":"Fons","sequence":"first","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, King's College London Faculty of Dentistry Oral & Craniofacial Sciences 1 , London SE1 9RT ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, King's College London Faculty of Dentistry Oral & Craniofacial Sciences 1 , London SE1 9RT ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0649-1432","authenticated-orcid":false,"given":"Roman H.","family":"Khonsari","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker \u2013 Enfants Malades 2 Service de Chirurgie maxillofaciale et Chirurgie plastique , , 149 rue de S\u00e8vres, 75015 Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8871-6094","authenticated-orcid":false,"given":"Abigail S.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, King's College London Faculty of Dentistry Oral & Craniofacial Sciences 1 , London SE1 9RT ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"2026020608284503800_DEV204784C1","doi-asserted-by":"publisher","first-page":"4613","DOI":"10.1242\/dev.129.19.4613","article-title":"Fgf8 is required for pharyngeal arch and cardiovascular development in the mouse","volume":"129","author":"Abu-Issa","year":"2002","journal-title":"Development"},{"key":"2026020608284503800_DEV204784C2","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1136\/jmg.2008.062158","article-title":"Genetics of microtia and associated syndromes","volume":"46","author":"Alasti","year":"2009","journal-title":"J. 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