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Publication : An endothelin-1 switch specifies maxillomandibular identity.

First Author  Sato T Year  2008
Journal  Proc Natl Acad Sci U S A Volume  105
Issue  48 Pages  18806-11
PubMed ID  19017795 Mgi Jnum  J:224515
Mgi Id  MGI:5688194 Doi  10.1073/pnas.0807345105
Citation  Sato T, et al. (2008) An endothelin-1 switch specifies maxillomandibular identity. Proc Natl Acad Sci U S A 105(48):18806-11
abstractText  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.
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