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Loss of function of <jats:italic>Foxc2<\/jats:italic> causes craniofacial abnormalities such as cleft palate and deformed cranial base, but its role during craniofacial development remains to be elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The contributions of <jats:italic>Foxc2<\/jats:italic>\u2010positive and its descendant cells to the craniofacial structure at E18.5 were examined using a tamoxifen\u2010inducible Cre driver mouse (<jats:italic>Foxc2\u2010CreERT2<\/jats:italic>) crossed with the <jats:italic>R26R\u2010LacZ<\/jats:italic> reporter mouse. <jats:italic>Foxc2<\/jats:italic> expression at E8.5 is restricted to the cranial mesenchyme, contributing to specific components including the cranial base, sensory capsule, tongue, upper incisor, and middle ear. Expression at E10.5 was still positively regulated in most of those regions. In situ hybridization analysis of <jats:italic>Foxc2<\/jats:italic> and its closely related gene, <jats:italic>Foxc1<\/jats:italic>, revealed that expression domains of these genes largely overlap in the cephalic mesenchyme. Meanwhile, the tongue expressed <jats:italic>Foxc2<\/jats:italic> but not <jats:italic>Foxc1<\/jats:italic>, and its development was affected by the neural crest\u2010specific deletion of <jats:italic>Foxc2<\/jats:italic> in mice (<jats:italic>Wnt1\u2010Cre; Foxc2<\/jats:italic><jats:sup><jats:italic>fl\/fl<\/jats:italic><\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>Foxc2<\/jats:italic> is expressed in cranial mesenchyme that contributes to specific craniofacial tissue components from an early stage, and it seems to be involved in their development in cooperation with <jats:italic>Foxc1<\/jats:italic>. <jats:italic>Foxc2<\/jats:italic> also has its own role in tongue development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.324","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T10:02:38Z","timestamp":1614938558000},"page":"1125-1139","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cell lineage\u2010 and expression\u2010based inference of the roles of forkhead box transcription factor <scp><i>Foxc2<\/i><\/scp> in craniofacial development"],"prefix":"10.1002","volume":"250","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4284-1479","authenticated-orcid":false,"given":"Manami","family":"Takenoshita","sequence":"first","affiliation":[{"name":"Department of Molecular Craniofacial Embryology, Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University (TMDU)  Tokyo Japan"},{"name":"Department of Pediatric Dentistry and Special Needs Dentistry, Graduate School of Medical and Dental Sciences Tokyo Medical and Dental 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