Bmp 信号在心脏发育过程中以剂量依赖的方式调节 Hand1。

Bmp Signaling Regulates Hand1 in a Dose-Dependent Manner during Heart Development.

机构信息

Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

出版信息

Int J Mol Sci. 2021 Sep 11;22(18):9835. doi: 10.3390/ijms22189835.

DOI:10.3390/ijms22189835

PMID:34576009

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8465227/

Abstract

The bone morphogenetic protein (Bmp) signaling pathway and the basic helix-loop-helix (bHLH) transcription factor Hand1 are known key regulators of cardiac development. In this study, we investigated the Bmp signaling regulation of during cardiac outflow tract (OFT) development. In and loss-of-function embryos with varying levels of in the heart, is sensitively decreased in response to the dose of expression. In contrast, in the heart is dramatically increased in gain-of-function embryos. We further identified and characterized the Bmp/Smad regulatory elements in . Combined transfection assays and chromatin immunoprecipitation (ChIP) experiments indicated that is directly activated and bound by Smads. In addition, we found that upon the treatment of Bmp2 and Bmp4, P19 cells induced Hand1 expression and favored cardiac differentiation. Together, our data indicated that the Bmp signaling pathway directly regulates expression in a dose-dependent manner during heart development.

摘要

骨形态发生蛋白（Bmp）信号通路和碱性螺旋-环-螺旋（bHLH）转录因子 Hand1 是心脏发育的关键调节因子。在这项研究中，我们研究了 Bmp 信号通路对心脏流出道（OFT）发育过程中表达的调节作用。在和心脏中不同水平的功能丧失的胚胎中，的表达水平对的剂量变化非常敏感。相反，在功能获得的胚胎中，的表达水平显著增加。我们进一步鉴定并描述了中的 Bmp/Smad 调节元件。联合转染实验和染色质免疫沉淀（ChIP）实验表明，Smads 直接激活并结合。此外，我们发现，在 Bmp2 和 Bmp4 处理后，P19 细胞诱导 Hand1 表达并促进心脏分化。综上所述，我们的数据表明，Bmp 信号通路在心脏发育过程中以剂量依赖的方式直接调节的表达。