title: Specification of jaw identity by the Hand2 transcription factor.
abstract: Acquisition of the lower jaw (mandible) was evolutionarily important for jawed vertebrates. In humans, syndromic craniofacial malformations often accompany jaw anomalies. The basic helix-loop-helix transcription factor Hand2, which is conserved among jawed vertebrates, is expressed in the neural crest in the mandibular process but not in the maxillary process of the first branchial arch. Here, we provide evidence that Hand2 is sufficient for upper jaw (maxilla)-to-mandible transformation by regulating the expression of homeobox transcription factors in mice. Altered Hand2 expression in the neural crest transformed the maxillae into mandibles with duplicated Meckel's cartilage, which resulted in an absence of the secondary palate. In Hand2-overexpressing mutants, non-Hox homeobox transcription factors were dysregulated. These results suggest that Hand2 regulates mandibular development through downstream genes of Hand2 and is therefore a major determinant of jaw identity. Hand2 may have influenced the evolutionary acquisition of the mandible and secondary palate.
authors.affiliation: Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Funato
authors.affiliation: Division of Mammalian Development, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.|Department of Genetics, The Graduate University for Advanced Studies, Yata 1111, Mishima, Shizuoka 411-8540, Japan.|Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima 734-8551, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kokubo
authors.affiliation: Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9148, USA.|Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yanagisawa
authors.affiliation: Division of Mammalian Development, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.|Department of Genetics, The Graduate University for Advanced Studies, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D006801:Humans; D008334:Mandible / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D009432:Neural Crest / Q000254:growth & development* / Q000378:metabolism; D010159:Palate / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014157:Transcription Factors; C498766:Hand2 protein, mouse