Endothelin-1 regulates the dorsoventral branchial arch patterning in mice.
Endothelin-1 (ET-1), a 21-amino acid peptide secreted by the epithelium and core mesenchyme in the branchial arches as well as vascular endothelium, is involved in craniofacial and cardiovascular development through endothelin receptor type-A (EdnrA) expressed in the neural crest-derived ectomesenchyme. Here we show that ET-1(-/-) mutant mice exhibit a homeotic-like transformation of the lower jaw to an upper jaw. Most of the maxillary arch-derived components are duplicated and replaced mandibular arch-derived structures, resulting in a mirror image of the upper and lower jaws in the ET-1(-/-) mutant. As for hyoid arch-derivatives, the ventral structures are severely affected in comparison to the dorsal ones in the ET-1(-/-) mutant. Correspondingly, the expression of Dlx5 and Dlx6, Distalless-related homeobox genes determining the ventral identity of the anterior branchial arches, and of the mandibular marker gene Pitx1 is significantly downregulated in the ET-1(-/-) mutant, whereas the expression of Dlx2 and the maxillary marker gene Prx2 is unaffected or rather upregulated. These findings indicate that the ET-1/EdnrA signaling may contribute to the dorsoventral axis patterning of the branchial arch system as a mediator of the regional intercellular interactions.
Ozeki
Hidenori
H
Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kurihara
Yukiko
Y
Tonami
Kazuo
K
Watatani
Sanae
S
Kurihara
Hiroki
H
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D001934:Branchial Region / Q000196:embryology* / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D017403:In Situ Hybridization; D008334:Mandible / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology; D051379:Mice / Q000196:embryology*; D009154:Mutation; D010641:Phenotype
D019332:Endothelin-1