Anderson Ryan M, Stottmann Rolf W, Choi Murim, Klingensmith John
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Dev Dyn. 2006 Sep;235(9):2507-20. doi: 10.1002/dvdy.20891.
We demonstrate here that Chordin and Noggin function as bone morphogenetic protein (BMP) antagonists in vivo to promote mammalian neural crest development. Using Chrd and Nog single and compound mutants, we find that Noggin has a major role in promoting neural crest formation, in which Chordin is partially redundant. BMP signaling is increased in dorsal tissues lacking Noggin and is further increased when Chordin is also absent. The early neural crest domain is expanded with decreased BMP antagonism in vivo. Noggin and Chordin also regulate subsequent neural crest cell emigration from the neural tube. However, reduced levels of these BMP antagonists ultimately result in perturbation of neural crest cell derived peripheral nervous system and craniofacial skeletal elements. Such defects reflect, at least in part, a function to limit apoptosis in neural crest cells. Noggin and Chordin, therefore, function together to regulate both the generation and survival of neural crest cells in mammalian development.
我们在此证明，腱蛋白（Chordin）和头蛋白（Noggin）在体内作为骨形态发生蛋白（BMP）拮抗剂发挥作用，以促进哺乳动物神经嵴的发育。利用Chrd和Nog单突变体及复合突变体，我们发现头蛋白在促进神经嵴形成中起主要作用，其中腱蛋白部分冗余。在缺乏头蛋白的背侧组织中BMP信号增强，当腱蛋白也缺失时则进一步增强。体内早期神经嵴区域随着BMP拮抗作用降低而扩大。头蛋白和腱蛋白还调节神经嵴细胞随后从神经管迁出。然而，这些BMP拮抗剂水平降低最终导致神经嵴细胞衍生的周围神经系统和颅面骨骼元件受到干扰。此类缺陷至少部分反映了其限制神经嵴细胞凋亡的功能。因此，头蛋白和腱蛋白共同作用，在哺乳动物发育过程中调节神经嵴细胞的产生和存活。
