TGF-β mediated Msx2 expression controls occipital somites-derived caudal region of skull development
TGF-β mediated Msx2 expression controls occipital somites-derived caudal region of skull development
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DOI：
10.1016/j.ydbio.2007.07.038
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发表时间：
2007-10-01
影响因子：
2.7
通讯作者：
Chai, Yang
中科院分区：
文献类型：
--
作者：
Hosokawa, Ryoichi;Urata, Mark;Chai, Yang
颅面发育包括颅神经脊和中胚层来源的细胞。转化生长因子-β信号在引导细胞形成颅面部骨骼过程中起着关键作用。然而，目前尚不清楚转化生长因子-β信号如何在颅面发育过程中调节中胚层来源的细胞的命运。在这项研究中，我们表明枕骨体节对哺乳动物头骨发育的尾部区域有贡献。在中胚层来源的细胞中，TGFBR2的条件失活会导致枕上骨的缺陷和脑膜脑膨出，以及C I椎体神经弓的中断。在细胞水平上，转化生长因子-β信号的缺失导致软骨细胞增殖减少和软骨向骨的过早分化。在TGFBR2突变体中，背腹轴形成的关键因子MSX2的表达减弱。值得注意的是，在Myf5-Cre；TGFBR2(FLOX/FLOX)小鼠中过表达MSX2部分挽救了枕上骨的发育。这些结果表明，转化生长因子-β/MSX2信号级联对颅骨尾部的发育至关重要。(C)2007 Elsevier Inc.保留所有权利。
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 C I 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;Tgfbr2(flox/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. (C) 2007 Elsevier Inc. All rights reserved.