TGF-beta mediated Msx2 expression controls occipital somites-derived caudal region of skull development.
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.
Hosokawa
Ryoichi
R
Center for Craniofacial Molecular Biology, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA.
Urata
Mark
M
Han
Jun
J
Zehnaly
Armen
A
Bringas
Pablo
P
Nonaka
Kazuaki
K
Chai
Yang
Y
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*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D016212:Transforming Growth Factor beta