Bmp Signaling Regulates Hand1 in a Dose-Dependent Manner during Heart Development.
Int J Mol Sci
; 22(18)2021 Sep 11.
Article
in En
| MEDLINE
| ID: mdl-34576009
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 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Organogenesis
/
Embryo, Mammalian
/
Basic Helix-Loop-Helix Transcription Factors
/
Bone Morphogenetic Protein 2
/
Bone Morphogenetic Protein 4
/
Heart
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Int J Mol Sci
Year:
2021
Type:
Article
Affiliation country:
United States