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XB-ART-2382
Genes Dev. February 1, 2005; 19 (3): 387-96.

Heart induction by Wnt antagonists depends on the homeodomain transcription factor Hex.



Abstract
Inhibition of canonical Wnt/beta-catenin signaling by Dickkopf-1 (Dkk-1) or Crescent initiates cardiogenesis in vertebrate embryos. However, nearly nothing is known about the downstream effectors of these secreted Wnt antagonists or the mechanism by which they activate heart formation. Here we show that Wnt antagonists in Xenopus stimulate cardiogenesis non-cell-autonomously, up to several cells away from those in which canonical Wnt/beta-catenin signaling is blocked, indicative of an indirect role in heart induction. A screen for downstream mediators revealed that Dkk-1 and other inhibitors of the canonical Wnt pathway induce the homeodomain transcription factor Hex, which is normally expressed in endoderm underlying the presumptive cardiac mesoderm in amphibian, bird, and mammalian embryos. Loss of Hex function blocks both endogenous heart development and ectopic heart induction by Dkk-1. As with the canonical Wnt pathway antagonists, ectopic Hex induces expression of cardiac markers non-cell-autonomously. Thus, to initiate cardiogenesis, Wnt antagonists act on endoderm to up-regulate Hex, which, in turn, controls production of a diffusible heart-inducing factor. This novel function for Hex suggests an etiology for the cardiac malformations in Hex mutant mice and will make possible the isolation of factors that induce heart directly in the mesoderm.

PubMed ID: 15687261
PMC ID: PMC546516
Article link: Genes Dev.
Grant support: F32 HL69595 NHLBI NIH HHS , R01 HL59502 NHLBI NIH HHS , R01 HL67079 NHLBI NIH HHS , R01 HL67079 NHLBI NIH HHS , R01 HL059502 NHLBI NIH HHS , R01 HL067079 NHLBI NIH HHS , F32 HL069595 NHLBI NIH HHS , R01 HL59502 NHLBI NIH HHS , F32 HL69595 NHLBI NIH HHS

Genes referenced: dkk1 frzb2 gsk3b hhex mapk8 nkx2-5 nodal tbx5 tnni3

Morpholinos referenced: hhex MO1

References:
Aoki, 2002, Pubmed[+]


Article Images: [+] show captions

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