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von Both, I.* ; Silvestri, C.* ; Erdemir, T.* ; Lickert, H.* ; Walls, J.R.* ; Henkelman, R.M.* ; Rossant, J.* ; Harvey, R.P.* ; Attisano, L.* ; Wrana, J.L.*

Foxh1 is essential for development of the anterior heart field.

Dev. Cell 7, 331-345 (2004)
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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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Zeitschrift Developmental Cell
Quellenangaben Band: 7, Heft: 3, Seiten: 331-345 Artikelnummer: , Supplement: ,
Verlag Elsevier
Begutachtungsstatus Peer reviewed