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骨形态发生蛋白在心肌生成诱导中的作用。

A role for bone morphogenetic proteins in the induction of cardiac myogenesis.

作者信息

Schultheiss T M, Burch J B, Lassar A B

机构信息

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Genes Dev. 1997 Feb 15;11(4):451-62. doi: 10.1101/gad.11.4.451.

Abstract

Little is known about the molecular mechanisms that govern heart specification in vertebrates. Here we demonstrate that bone morphogenetic protein (BMP) signaling plays a central role in the induction of cardiac myogenesis in the chick embryo. At the time when chick precardiac cells become committed to the cardiac muscle lineage, they are in contact with tissues expressing BMP-2, BMP-4, and BMP-7. Application of BMP-2-soaked beads in vivo elicits ectopic expression of the cardiac transcription factors CNkx-2.5 and GATA-4. Furthermore, administration of soluble BMP-2 or BMP-4 to explant cultures induces full cardiac differentiation in stage 5 to 7 anterior medial mesoderm, a tissue that is normally not cardiogenic. The competence to undergo cardiogenesis in response to BMPs is restricted to mesoderm located in the anterior regions of gastrula- to neurula-stage embryos. The secreted protein noggin, which binds to BMPs and antagonizes BMP activity, completely inhibits differentiation of the precardiac mesoderm, indicating that BMP activity is required for myocardial differentiation in this tissue. Together, these data imply that a cardiogenic field exists in the anterior mesoderm and that localized expression of BMPs selects which cells within this field enter the cardiac myocyte lineage.

摘要

关于脊椎动物心脏特化的分子机制,人们了解甚少。在此,我们证明骨形态发生蛋白(BMP)信号在鸡胚心肌发生的诱导过程中起着核心作用。在鸡胚前心脏细胞开始确定向心肌谱系分化时,它们与表达BMP - 2、BMP - 4和BMP - 7的组织接触。在体内应用浸泡有BMP - 2的珠子可引发心脏转录因子CNkx - 2.5和GATA - 4的异位表达。此外,向体外培养的组织块中添加可溶性BMP - 2或BMP - 4可诱导处于5至7期的前内侧中胚层(一种通常不具有心脏发生能力的组织)实现完全的心脏分化。对BMP作出反应而进行心脏发生的能力仅限于原肠胚到神经胚阶段胚胎前部区域的中胚层。分泌蛋白头蛋白可与BMP结合并拮抗BMP活性,它能完全抑制前心脏中胚层的分化,这表明BMP活性是该组织中心肌分化所必需的。这些数据共同表明,在前中胚层中存在一个心脏发生场域,并且BMP的局部表达决定了该场域内哪些细胞进入心肌细胞谱系。

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