Hand2 function in second heart field progenitors is essential for cardiogenesis

Takatoshi Tsuchihashi, Jun Maeda, Chong H. Shin, Kathryn N. Ivey, Brian L. Black, Eric N. Olson, Hiroyuki Yamagishi, Deepak Srivastava

研究成果: Article査読

70 被引用数 (Scopus)

抄録

Cardiogenesis involves the contributions of multiple progenitor pools, including mesoderm-derived cardiac progenitors known as the first and second heart fields. Disruption of genetic pathways regulating individual subsets of cardiac progenitors likely underlies many forms of human cardiac malformations. Hand2 is a member of the basic helix loop helix (bHLH) family of transcription factors and is expressed in numerous cell lineages that contribute to the developing heart. However, the early embryonic lethality of Hand2-null mice has precluded lineage-specific study of its function in myocardial progenitors. Here, we generated and used a floxed allele of Hand2 to ablate its expression in specific cardiac cell populations at defined developmental points. We found that Hand2 expression within the mesoderm-derived second heart field progenitors was required for their survival and deletion in this domain recapitulated the complete Hand2-null phenotype. Loss of Hand2 at later stages of development and in restricted domains of the second heart field revealed a spectrum of cardiac anomalies resembling forms of human congenital heart disease. Molecular analyses of Hand2 mutant cells revealed several genes by which Hand2 may influence expansion of the cardiac progenitors. These findings demonstrate that Hand2 is essential for survival of second heart field progenitors and that the graded loss of Hand2 function in this cardiac progenitor pool can cause a spectrum of congenital heart malformation.

本文言語English
ページ(範囲)62-69
ページ数8
ジャーナルDevelopmental Biology
351
1
DOI
出版ステータスPublished - 2011 3 1

ASJC Scopus subject areas

  • 分子生物学
  • 発生生物学
  • 細胞生物学

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