[PDF][PDF] Foxh1 is essential for development of the anterior heart field

I von Both, C Silvestri, T Erdemir, H Lickert, JR Walls… - Developmental cell, 2004 - cell.com
Developmental cell, 2004cell.com
The anterior heart field (AHF) mediates formation of the outflow tract (OFT) and right ventricle
(RV) during looping morphogenesis of the heart. Foxh1 is a forkhead DNA binding
transcription factor in the TGFβ-Smad pathway. Here we demonstrate that Foxh1−/− mutant
mouse embryos form a primitive heart tube, but fail to form OFT and RV and display loss of
outer curvature markers of the future working myocardium, similar to the phenotype of
Mef2c−/− mutant hearts. Further, we show that Mef2c is a direct target of Foxh1, which …
Abstract
The anterior heart field (AHF) mediates formation of the outflow tract (OFT) and right ventricle (RV) during looping morphogenesis of the heart. Foxh1 is a forkhead DNA binding transcription factor in the TGFβ-Smad pathway. Here we demonstrate that Foxh1−/− mutant mouse embryos form a primitive heart tube, but fail to form OFT and RV and display loss of outer curvature markers of the future working myocardium, similar to the phenotype of Mef2c−/− mutant hearts. Further, we show that Mef2c is a direct target of Foxh1, which physically and functionally interacts with Nkx2-5 to mediate strong Smad-dependent activation of a TGFβ response element in the Mef2c gene. This element directs transgene expression to the presumptive AHF, as well as the RV and OFT, a pattern that closely parallels endogenous Mef2c expression in the heart. Thus, Foxh1 and Nkx2-5 functionally interact and are essential for development of the AHF and its derivatives, the RV and OFT, in response to TGFβ-like signals.
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