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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development
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Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development

机译：心肌神经rest需要心肌相关转录因子B，以促进平滑肌分化和心血管发育

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摘要

Members of the myocardin-related family of transcription factors play critical roles in regulating vascular smooth muscle and cardiac differentiation. To examine the function of myocardin-related transcription factor (MRTF)-B, mice were generated from ES cells harboring a conditional insertional mutation, or gene trap, of the MRTF-B gene. Expression of the MRTF-B mutant allele results in a fusion protein consisting of the N terminus of MRTF-B fused to p-galactosidase, which is functionally null. Homozygous MRTF-B gene trap mice (MRTF-B-/-) die between embryonic day (E)17.5 and postnatal day 1 from cardiac outflow tract defects. MRTF-B is expressed in the premigratory neural crest, in rhombomeres 3 and 5, and in the neural crest-derived mesenchyme surrounding the aortic arch arteries. Consistent with the pattern of expression, E10.5 and E11.5 MRTF-B-/- mutants exhibit deformation of aortic arch arteries 3, 4, and 6 and severe attenuation of smooth muscle cell differentiation in the arch arteries and the aorticopulmonary septum, despite normal migration and initial patterning of cardiac neural crest cells. Remarkably, the observed pathology was rescued and viable mice generated by intercrossing MRTF-B mutants with mice expressing Cre recombinase under the transcriptional control of the neural crest-restricted Wnt-1 promoter, which results in restoration of normal MRTF-B expression in the neural crest. Taken together, these studies reveal that MRTF-B plays a critical role in regulating differentiation of cardiac neural crest cells into smooth muscle and demonstrate that neural crest-derived smooth muscle differentiation is specifically required for normal cardiovascular morphogenesis.
机译：心肌相关转录因子家族成员在调节血管平滑肌和心脏分化中起关键作用。为了检查心肌相关转录因子（MRTF）-B的功能，从具有MRTF-B基因的条件插入突变或基因陷阱的ES细胞中产生了小鼠。 MRTF-B突变等位基因的表达产生了融合蛋白，该融合蛋白由与p-半乳糖苷酶融合的MRTF-B的N端组成，在功能上无效。纯合子MRTF-B基因陷阱小鼠（MRTF-B-/-）在胚胎第（E）17.5天和出生后第1天之间因心脏流出道缺陷而死亡。 MRTF-B在迁徙前的神经,、菱形3和5中以及在主动脉弓周围的神经me衍生的间充质中表达。与表达模式一致，E10.5和E11.5 MRTF-B-/-突变体表现出主动脉弓3、4和6的变形，并严重减弱了弓动脉和主肺隔的平滑肌细胞分化，尽管正常迁移和心脏神经c细胞的初始模式。值得注意的是，挽救了观察到的病理，并通过在神经rest限制性Wnt-1启动子的转录控制下使MRTF-B突变体与表达Cre重组酶的小鼠杂交而产生了活体小鼠，从而恢复了神经中正常MRTF-B的表达。波峰。综上所述，这些研究表明MRTF-B在调节心脏神经rest细胞向平滑肌的分化中起着至关重要的作用，并表明神经-衍生的平滑肌的分化是正常心血管形态发生的特殊要求。

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