First Author | von Both I | Year | 2004 |
Journal | Dev Cell | Volume | 7 |
Issue | 3 | Pages | 331-45 |
PubMed ID | 15363409 | Mgi Jnum | J:93034 |
Mgi Id | MGI:3055632 | Doi | 10.1016/j.devcel.2004.07.023 |
Citation | von Both I, et al. (2004) Foxh1 is essential for development of the anterior heart field. Dev Cell 7(3):331-45 |
abstractText | 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 TGFbeta-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 TGFbeta 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 TGFbeta-like signals. |