title: An endothelin-1 switch specifies maxillomandibular identity.
abstract: Articulated jaws are highly conserved structures characteristic of gnathostome evolution. Epithelial-mesenchymal interactions within the first pharyngeal arch (PA1) instruct cephalic neural crest cells (CNCCs) to form the different skeletal elements of the jaws. The endothelin-1 (Edn1)/endothelin receptor type-A (Ednra)-->Dlx5/6-->Hand2 signaling pathway is necessary for lower jaw formation. Here, we show that the Edn1 signaling is sufficient for the conversion of the maxillary arch to mandibular identity. Constitutive activation of Ednra induced the transformation of upper jaw, maxillary, structures into lower jaw, mandibular, structures with duplicated Meckel's cartilage and dermatocranial jaws constituted by 4 dentary bones. Misexpression of Hand2 in the Ednra domain caused a similar transformation. Skeletal transformations are accompanied by neuromuscular remodeling. Ednra is expressed by most CNCCs, but its constitutive activation affects predominantly PA1. We conclude that after migration CNCCs are not all equivalent, suggesting that their specification occurs in sequential steps. Also, we show that, within PA1, CNCCs are competent to form both mandibular and maxillary structures and that an Edn1 switch is responsible for the choice of either morphogenetic program.
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sato
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Rieko
authors.initials: R
authors.lastname: Asai
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tonami
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Uchijima
authors.forename: Eglantine
authors.initials: E
authors.lastname: Heude
authors.forename: Marc
authors.initials: M
authors.lastname: Ekker
authors.forename: Giovanni
authors.initials: G
authors.lastname: Levi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D019521:Body Patterning; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008334:Mandible / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D008437:Maxilla / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019332:Endothelin-1; D044022:Receptor, Endothelin A; C498766:Hand2 protein, mouse