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Fgf8 is required for anterior heart field development.

Publication ,  Journal Article
Ilagan, R; Abu-Issa, R; Brown, D; Yang, Y-P; Jiao, K; Schwartz, RJ; Klingensmith, J; Meyers, EN
Published in: Development
June 2006

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.

Duke Scholars

Published In

Development

DOI

ISSN

0950-1991

Publication Date

June 2006

Volume

133

Issue

12

Start / End Page

2435 / 2445

Location

England

Related Subject Headings

  • Transcription Factors
  • Signal Transduction
  • Neural Crest
  • Mice, Knockout
  • Mice
  • Mesoderm
  • In Situ Hybridization
  • Homeodomain Proteins
  • Heart
  • Genes, Reporter
 

Citation

APA
Chicago
ICMJE
MLA
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Ilagan, R., Abu-Issa, R., Brown, D., Yang, Y.-P., Jiao, K., Schwartz, R. J., … Meyers, E. N. (2006). Fgf8 is required for anterior heart field development. Development, 133(12), 2435–2445. https://doi.org/10.1242/dev.02408
Ilagan, Roger, Radwan Abu-Issa, Doris Brown, Yu-Ping Yang, Kai Jiao, Robert J. Schwartz, John Klingensmith, and Erik N. Meyers. “Fgf8 is required for anterior heart field development.Development 133, no. 12 (June 2006): 2435–45. https://doi.org/10.1242/dev.02408.
Ilagan R, Abu-Issa R, Brown D, Yang Y-P, Jiao K, Schwartz RJ, et al. Fgf8 is required for anterior heart field development. Development. 2006 Jun;133(12):2435–45.
Ilagan, Roger, et al. “Fgf8 is required for anterior heart field development.Development, vol. 133, no. 12, June 2006, pp. 2435–45. Pubmed, doi:10.1242/dev.02408.
Ilagan R, Abu-Issa R, Brown D, Yang Y-P, Jiao K, Schwartz RJ, Klingensmith J, Meyers EN. Fgf8 is required for anterior heart field development. Development. 2006 Jun;133(12):2435–2445.
Journal cover image

Published In

Development

DOI

ISSN

0950-1991

Publication Date

June 2006

Volume

133

Issue

12

Start / End Page

2435 / 2445

Location

England

Related Subject Headings

  • Transcription Factors
  • Signal Transduction
  • Neural Crest
  • Mice, Knockout
  • Mice
  • Mesoderm
  • In Situ Hybridization
  • Homeodomain Proteins
  • Heart
  • Genes, Reporter