TY - JOUR
T1 - TGF-β mediated Msx2 expression controls occipital somites-derived caudal region of skull development
AU - Hosokawa, Ryoichi
AU - Urata, Mark
AU - Han, Jun
AU - Zehnaly, Armen
AU - Bringas, Pablo
AU - Nonaka, Kazuaki
AU - Chai, Yang
N1 - Funding Information:
We thank Julie Mayo, Mamoru Ishii, and Brauch Frenkel for critical reading of the manuscript. We also thank J.L.R. Rubenstein for reagents; H. Moses for the Tgfbr2 fl/fl mice, Philippe Soriano for Myf5-Cre and Rob Maxson for Msx2 TG/+ mice. This study was supported by grants from the National Institute of Dental and Craniofacial Research, NIH (DE017007, DE012711, and DE014078) and March of Dimes Birth Defect Foundation (#6-FY05-67) to Yang Chai.
PY - 2007/10/1
Y1 - 2007/10/1
N2 - Craniofacial development involves cranial neural crest (CNC) and mesoderm-derived cells. TGF-β signaling plays a critical role in instructing CNC cells to form the craniofacial skeleton. However, it is not known how TGF-β 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-β 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-β/Msx2 signaling cascade is critical for development of the caudal region of the skull.
AB - Craniofacial development involves cranial neural crest (CNC) and mesoderm-derived cells. TGF-β signaling plays a critical role in instructing CNC cells to form the craniofacial skeleton. However, it is not known how TGF-β 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-β 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-β/Msx2 signaling cascade is critical for development of the caudal region of the skull.
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U2 - 10.1016/j.ydbio.2007.07.038
DO - 10.1016/j.ydbio.2007.07.038
M3 - Article
C2 - 17727833
AN - SCOPUS:34548853994
SN - 0012-1606
VL - 310
SP - 140
EP - 153
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -