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

First Author  Zheng M Year  2021
Journal  Int J Mol Sci Volume  22
Issue  18 PubMed ID  34576009
Mgi Jnum  J:310871 Mgi Id  MGI:6764214
Doi  10.3390/ijms22189835 Citation  Zheng M, et al. (2021) Bmp Signaling Regulates Hand1 in a Dose-Dependent Manner during Heart Development. Int J Mol Sci 22(18)
abstractText  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 Hand1 during cardiac outflow tract (OFT) development. In Bmp2 and Bmp4loss-of-function embryos with varying levels of Bmp in the heart, Hand1 is sensitively decreased in response to the dose of Bmp expression. In contrast, Hand1 in the heart is dramatically increased in Bmp4 gain-of-function embryos. We further identified and characterized the Bmp/Smad regulatory elements in Hand1. Combined transfection assays and chromatin immunoprecipitation (ChIP) experiments indicated that Hand1 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 Hand1 expression in a dose-dependent manner during heart development.
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