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We have utilised multiple genetic approaches to investigate local temporospatial requirements for sonic hedgehog (SHH) signalling during tongue development. Mice lacking a Shh cis-enhancer, MFCS4 (ShhMFCS4\/\u2212), with reduced SHH in dorsal tongue epithelium have perturbed lingual septum tendon formation and disrupted intrinsic muscle patterning, with these defects reproduced following global Shh deletion from E10.5 in pCag-CreERTM; Shhflox\/flox embryos. SHH responsiveness was diminished in local cranial neural crest cell (CNCC) populations in both mutants, with SHH targeting these cells through the primary cilium. CNCC-specific deletion of orofaciodigital syndrome 1 (Ofd1), which encodes a ciliary protein, in Wnt1-Cre; Ofdfl\/Y mice led to a complete loss of normal myotube arrangement and hypoglossia. In contrast, mesoderm-specific deletion of Ofd1 in Mesp1-Cre; Ofdfl\/Y embryos resulted in normal intrinsic muscle arrangement. Collectively, these findings suggest key temporospatial requirements for local SHH signalling in tongue development (specifically, lingual tendon differentiation and intrinsic muscle patterning through signalling to CNCCs) and provide further mechanistic insight into the tongue anomalies seen in patients with disrupted hedgehog signalling.<\/jats:p>","DOI":"10.1242\/dev.180075","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T09:29:13Z","timestamp":1573550953000},"source":"Crossref","is-referenced-by-count":19,"title":["Temporospatial sonic hedgehog signalling is essential for neural crest-dependent patterning of the intrinsic tongue musculature"],"prefix":"10.1242","volume":"146","author":[{"given":"Shigeru","family":"Okuhara","sequence":"first","affiliation":[{"name":"Section of Molecular Craniofacial Embryology, Graduate School of Dental and Medical Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anahid A.","family":"Birjandi","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeel","family":"Adel Al-Lami","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Sagai","sequence":"additional","affiliation":[{"name":"Mammalian Genetics Laboratory, National Institute of Genetics, Mishima 411-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Amano","sequence":"additional","affiliation":[{"name":"Mammalian Genetics Laboratory, National Institute of Genetics, Mishima 411-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Shiroishi","sequence":"additional","affiliation":[{"name":"Mammalian Genetics Laboratory, National Institute of Genetics, Mishima 411-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme M.","family":"Xavier","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2483-2165","authenticated-orcid":false,"given":"Karen J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2857-0315","authenticated-orcid":false,"given":"Martyn T.","family":"Cobourne","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8448-9410","authenticated-orcid":false,"given":"Sachiko","family":"Iseki","sequence":"additional","affiliation":[{"name":"Section of Molecular Craniofacial Embryology, Graduate School of Dental and Medical Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,11,12]]},"reference":[{"key":"2021042622575606100_DEV180075C1","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1042\/BST20160241","article-title":"Micrognathia in mouse models of ciliopathies","volume":"44","author":"Adel Al-Lami","year":"2016","journal-title":"Biochem. 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