Fgf8 is required for anterior heart field development.

Published

Journal Article

In the mouse embryo, the splanchnic mesodermal cells of the anterior heart field (AHF) migrate from the pharynx to contribute to the early myocardium of the outflow tract (OT) and right ventricle (RV). Recent studies have attempted to distinguish the AHF from other precardiac populations, and to determine the genetic and molecular mechanisms that regulate its development. Here, we have used an Fgf8lacZ allele to demonstrate that Fgf8 is expressed within the developing AHF. In addition, we use both a hypomorphic Fgf8 allele (Fgf8neo) and Cre-mediated gene ablation to show that Fgf8 is essential for the survival and proliferation of the AHF. Nkx2.5Cre is expressed in the AHF, primary heart tube and pharyngeal endoderm, while TnT-Cre is expressed only within the specified heart tube myocardium. Deletion of Fgf8 by Nkx2.5Cre results in a significant loss of the Nkx2.5Cre lineage and severe OT and RV truncations by E9.5, while the remaining heart chambers (left ventricle and atria) are grossly normal. These defects result from significant decreases in cell proliferation and aberrant cell death in both the pharyngeal endoderm and splanchnic mesoderm. By contrast, ablation of Fgf8 in the TnT-Cre domain does not result in OT or RV defects, providing strong evidence that Fgf8 expression is crucial in the pharyngeal endoderm and/or overlying splanchnic mesoderm of the AHF at a stage prior to heart tube elongation. Analysis of downstream signaling components, such as phosphorylated-Erk and Pea3, identifies the AHF splanchnic mesoderm itself as a target for Fgf8 signaling.

Full Text

Duke Authors

Cited Authors

  • Ilagan, R; Abu-Issa, R; Brown, D; Yang, Y-P; Jiao, K; Schwartz, RJ; Klingensmith, J; Meyers, EN

Published Date

  • June 2006

Published In

Volume / Issue

  • 133 / 12

Start / End Page

  • 2435 - 2445

PubMed ID

  • 16720880

Pubmed Central ID

  • 16720880

Electronic International Standard Serial Number (EISSN)

  • 1477-9129

International Standard Serial Number (ISSN)

  • 0950-1991

Digital Object Identifier (DOI)

  • 10.1242/dev.02408

Language

  • eng