@article{ef688de2df944e9b8a8faffa06211439,
title = "Foxh1 is essential for development of the anterior heart field",
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.",
author = "{von Both}, Ingo and Cristoforo Silvestri and Tuba Erdemir and Heiko Lickert and Walls, {Johnathon R.} and Henkelman, {R. Mark} and Janet Rossant and Harvey, {Richard P.} and Liliana Attisano and Wrana, {Jeffrey L.}",
note = "Funding Information: The authors thank Michael Kl{\"u}ppel, Christine Le Roy, and Melanie Pye for advice and Benoit G. Bruneau for critical evaluation of the manuscript. We would like to thank the Transgenic Mouse Facility at Mount Sinai Hospital and Kendraprasad Harpal for advice and excellent technical assistance during this work, as well as Douglas Holmyard at the Advanced Bioimaging Centre at Mount Sinai Hospital for Scanning Electron Microscopy. For plasmids and cDNA probes we thank Rosa S. Beddington (BMP7), Benoit G. Bruneau (Nppa), Margaret Buckingham (Actc1), Kenneth R. Chien (Myl2), Sylvia Evans (Wnt11), Manfred Gessler (Hey2), Brigit L.M. Hogan (BMP2, Fgf10), Peter W. Laird (pPGKPuro), Gary E. Lyons (Myh6), Gail R. Martin (Fgf8), Eric N. Olson (Hand1), Virginia E. Papaioannou (Tbx5), Christine E. Seidman (Mybpc3), Austin Smith (pCAGIP), Deepak Srivastava (Hand2), and David B. Wilson (Gata4). This work was supported by grants to J.R., L.A., and J.L.W. from the Canadian Institutes of Health Research (CIHR) and to L.A. from the National Cancer Institute of Canada, with funds from the Canadian Cancer Society. I.v.B. was supported by the Koeln Fortune Program, Faculty of Medicine, University of Cologne and C.S. by a CIHR doctoral studentship. J.R. is a CIHR Distinguished Investigator, L.A. and J.L.W. are CIHR Investigators, and J.L.W. is an International Scholar of the Howard Hughes Medical Institute. ",
year = "2004",
month = sep,
doi = "10.1016/j.devcel.2004.07.023",
language = "English",
volume = "7",
pages = "331--345",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "3",
}