{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:33:41Z","timestamp":1790494421864,"version":"4.1.0"},"reference-count":56,"publisher":"The Company of Biologists","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"<jats:p>External ear abnormalities are frequent in newborns ranging from microtia to partial auricle duplication. Little is known about the molecular mechanisms orchestrating external ear morphogenesis. In humans, HOXA2 partial loss of function induces a bilateral microtia associated with an abnormal shape of the auricle. In mice, Hoxa2 inactivation at early gestational stages results in external auditory canal (EAC) duplication and absence of the auricle, whereas its late inactivation results in a hypomorphic auricle, mimicking the human HOXA2 mutant condition. By genetic fate mapping we found that the mouse auricle (or pinna) derives from the Hoxa2-expressing neural crest-derived mesenchyme of the second pharyngeal arch, and not from a composite of first and second arch mesenchyme as previously proposed based on morphological observation of human embryos. Moreover, the mouse EAC is entirely lined by Hoxa2-negative first arch mesenchyme and does not develop at the first pharyngeal cleft, as previously assumed. Conditional ectopic Hoxa2 expression in first arch neural crest is sufficient to induce a complete duplication of the pinna and a loss of the EAC, suggesting transformation of the first arch neural crest-derived mesenchyme lining the EAC into an ectopic pinna. Hoxa2 partly controls the morphogenesis of the pinna through the BMP signalling pathway and expression of Eya1, which in humans is involved in branchio-oto-renal syndrome. Thus, Hoxa2 loss- and gain-of-function approaches in mice provide a suitable model to investigate the molecular aetiology of microtia and auricle duplication.<\/jats:p>","DOI":"10.1242\/dev.098046","type":"journal-article","created":{"date-parts":[[2013,9,26]],"date-time":"2013-09-26T02:44:09Z","timestamp":1380163449000},"page":"4386-4397","source":"Crossref","is-referenced-by-count":94,"title":["Mouse <i>Hoxa2<\/i> mutations provide a model for microtia and auricle duplication"],"prefix":"10.1242","volume":"140","author":[{"given":"Maryline","family":"Minoux","sequence":"first","affiliation":[{"name":"Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland."},{"name":"INSERM UMR 1121, Universit\u00e9 de Strasbourg, Facult\u00e9 de Chirurgie Dentaire, 1, place de l\u2019h\u00f4pital, 67 000 Strasbourg, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudius F.","family":"Kratochwil","sequence":"additional","affiliation":[{"name":"Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland."},{"name":"University of Basel, CH-4056 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Ducret","sequence":"additional","affiliation":[{"name":"Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilu","family":"Amin","sequence":"additional","affiliation":[{"name":"School of Dentistry, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Kitazawa","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Bobola","sequence":"additional","affiliation":[{"name":"School of Dentistry, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Vilain","sequence":"additional","affiliation":[{"name":"Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo M.","family":"Rijli","sequence":"additional","affiliation":[{"name":"Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland."},{"name":"University of Basel, CH-4056 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042622161581500_R1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/ng0297-157","article-title":"A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family","volume":"15","author":"Abdelhak","year":"1997","journal-title":"Nat. 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