Frs2α-deficiency in cardiac progenitors disrupts a subset of FGF signals required for outflow tract morphogenesis

Jue Zhang, Yongshun Lin, Yongyou Zhang, Yongsheng Lan, Chunhong Lin, Anne M. Moon, Robert J. Schwartz, James F. Martin, Fen Wang

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


The cardiac outflow tract (OFT) is a developmentally complex structure derived from multiple lineages and is often defective in human congenital anomalies. Although emerging evidence shows that fibroblast growth factor (FGF) is essential for OFT development, the downstream pathways mediating FGF signaling in cardiac progenitors remain poorly understood. Here, we report that FRS2α (FRS2), an adaptor protein that links FGF receptor kinases to multiple signaling pathways, mediates crucial aspects of FGF-dependent OFT development in mouse. Ablation of Frs2α in mesodermal OFT progenitor cells that originate in the second heart field (SHF) affects their expansion into the OFT myocardium, resulting in OFT misalignment and hypoplasia. Moreover, Frs2α mutants have defective endothelial-to-mesenchymal transition and neural crest cell recruitment into the OFT cushions, resulting in OFT septation defects. These results provide new insight into the signaling molecules downstream of FGF receptor tyrosine kinases in cardiac progenitors.

Original languageEnglish (US)
Pages (from-to)3611-3622
Number of pages12
Issue number21
StatePublished - 2008


  • Cell signaling
  • Heart development
  • Mouse model
  • Receptor tyrosine kinase
  • Second heart field

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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