title: TGF-beta mediated Msx2 expression controls occipital somites-derived caudal region of skull development.
abstract: Craniofacial development involves cranial neural crest (CNC) and mesoderm-derived cells. TGF-beta signaling plays a critical role in instructing CNC cells to form the craniofacial skeleton. However, it is not known how TGF-beta signaling regulates the fate of mesoderm-derived cells during craniofacial development. In this study, we show that occipital somites contribute to the caudal region of mammalian skull development. Conditional inactivation of Tgfbr2 in mesoderm-derived cells results in defects of the supraoccipital bone with meningoencephalocele and discontinuity of the neural arch of the C1 vertebra. At the cellular level, loss of TGF-beta signaling causes decreased chondrocyte proliferation and premature differentiation of cartilage to bone. Expression of Msx2, a critical factor in the formation of the dorsoventral axis, is diminished in the Tgfbr2 mutant. Significantly, overexpression of Msx2 in Myf5-Cre;Tgfbr2flox/flox mice partially rescues supraoccipital bone development. These results suggest that the TGF-beta/Msx2 signaling cascade is critical for development of the caudal region of the skull.
authors.affiliation: Center for Craniofacial Molecular Biology, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Hosokawa
authors.forename: Mark
authors.initials: M
authors.lastname: Urata
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.forename: Armen
authors.initials: A
authors.lastname: Zehnaly
authors.forename: Pablo
authors.initials: P
authors.lastname: Bringas
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nonaka
authors.forename: Yang
authors.initials: Y
authors.lastname: Chai
mesh_terms: D000818:Animals; D020219:Chondrogenesis; D004268:DNA-Binding Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D051787:Myogenic Regulatory Factor 5 / Q000502:physiology; D009432:Neural Crest / Q000196:embryology; D015398:Signal Transduction; D012886:Skull / Q000196:embryology* / Q000502:physiology; D019170:Somites / Q000196:embryology; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D016212:Transforming Growth Factor beta