DNA binding-dependent and -independent functions of the Hand2 transcription factor during mouse embryogenesis

Ning Liu, Ana C. Barbosa, Shelby L. Chapman, Svetlana Bezprozvannaya, Xiaoxia Qi, James A. Richardson, Hiromi Yanagisawa, Eric N. Olson

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The basic helix-loop-helix (bHLH) transcription factor Hand2 is required for growth and development of the heart, branchial arches and limb buds. To determine whether DNA binding is required for Hand2 to regulate the growth and development of these different embryonic tissues, we generated mutant mice in which the Hand2 locus was modified by a mutation (referred to as Hand2EDE) that abolished the DNA-binding activity of Hand2, leaving the remainder of the protein intact. In contrast to Hand2 null embryos, which display right ventricular hypoplasia and vascular abnormalities, causing severe growth retardation by E9.5 and death by E10.5, early development of the heart appeared remarkably normal in homozygous Hand2EDE mutant embryos. These mutant embryos also lacked the early defects in growth of the branchial arches seen in Hand2 null embryos and survived up to 2 to 3 days longer than did Hand2 null embryos. However, Hand2EDE mutant embryos exhibited growth defects in the limb buds similar to those of Hand2 null embryos. These findings suggest that Hand2 regulates tissue growth and development in vivo through DNA binding-dependent and -independent mechanisms.

Original languageEnglish (US)
Pages (from-to)933-942
Number of pages10
JournalDevelopment
Volume136
Issue number6
DOIs
StatePublished - Mar 15 2009

Keywords

  • Craniofacial development
  • Hand2
  • Heart development
  • Limb development
  • bHLH

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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