G-Protein α-Subunit Gsα Is Required for Craniofacial Morphogenesis.
G-Protein α-Subunit Gsα Is Required for Craniofacial Morphogenesis.
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DOI：
10.1371/journal.pone.0147535
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Lei R;Zhang K;Wei Y;Chen M;Weinstein LS;Hong Y;Zhu M;Li H;Li H
异源三聚体G蛋白亚基Gsα偶联受体以激活腺苷酸环化酶，并且是细胞内cAMP反应和蛋白激酶A（PKA）激活所需的。Gsα在许多细胞类型中广泛表达;然而，Gsα在神经嵴细胞（NCC）中的作用仍不清楚。在这里，我们报告了NCCs特异性Gsα基因敲除小鼠在出生后数小时内死亡，并表现出严重的颅面畸形，包括上颌骨和下颌骨发育不良，腭裂和颅面骨骼缺陷。组织学和解剖学分析表明，Gsα基因敲除小鼠的腭裂是由颅面骨骼缺陷引起的继发性缺陷。在Gsα基因敲除小鼠中，NCCs来源的颅神经形态正常，但背根和交感神经节的发育受损。此外，在NCC中Gsα的缺失不影响颅NCC的迁移或细胞增殖，但显著加速骨软骨分化。综上所述，我们的研究表明Gsα是神经嵴细胞源性颅面发育所必需的。
The heterotrimeric G protein subunit Gsα couples receptors to activate adenylyl cyclase and is required for the intracellular cAMP response and protein kinase A (PKA) activation. Gsα is ubiquitously expressed in many cell types; however, the role of Gsα in neural crest cells (NCCs) remains unclear. Here we report that NCCs-specific Gsα knockout mice die within hours after birth and exhibit dramatic craniofacial malformations, including hypoplastic maxilla and mandible, cleft palate and craniofacial skeleton defects. Histological and anatomical analysis reveal that the cleft palate in Gsα knockout mice is a secondary defect resulting from craniofacial skeleton deficiencies. In Gsα knockout mice, the morphologies of NCCs-derived cranial nerves are normal, but the development of dorsal root and sympathetic ganglia are impaired. Furthermore, loss of Gsα in NCCs does not affect cranial NCCs migration or cell proliferation, but significantly accelerate osteochondrogenic differentiation. Taken together, our study suggests that Gsα is required for neural crest cells-derived craniofacial development.