Format

Send to

Choose Destination
See comment in PubMed Commons below
J Mol Cell Cardiol. 2010 Nov;49(5):836-40. doi: 10.1016/j.yjmcc.2010.08.023. Epub 2010 Aug 31.

Partial rescue of the Tbx1 mutant heart phenotype by Fgf8: genetic evidence of impaired tissue response to Fgf8.

Author information

  • 1Institute of Biosciences and Technologies, Texas A&M University, Houston, TX, USA.

Abstract

Tbx1 is the candidate gene of DiGeorge syndrome and is required in humans and mice for the development of the cardiac outflow tract (OFT) and aortic arch arteries. Loss of function mutants present with reduced cell proliferation and premature differentiation of cardiac progenitor cells of the second heart field (SHF). Tbx1 regulates Fgf8 expression hence the hypothesis that the proliferation impairment may contribute to the heart phenotype of mutants. Here we show that forced Fgf8 expression modifies and partially rescues the OFT septation defects of Tbx1 mutants but only if there is some residual expression of Tbx1. This genetic experiment suggests that Tbx1, directly or indirectly, affects tissue response to Fgf8. Indeed, Tbx1(-/-) mouse embryonic fibroblasts were unable to respond to Fgf8 added to the culture media and showed defective response of Erk1/2 and Rsk1. Our data suggest a coordinated pathway modulating Fgf8 ligand expression and tissue response to it in the SHF.

PMID:
20807544
PMCID:
PMC2981862
DOI:
10.1016/j.yjmcc.2010.08.023
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center