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Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart.

Human mutations in TBX5, a gene encoding a T-box transcription factor, and SALL4, a gene encoding a zinc-finger transcription factor, cause similar upper limb and heart defects. Here we show that Tbx5 regulates Sall4 expression in the developing mouse forelimb and heart; mice heterozygous for a gene trap allele of Sall4 show limb and heart defects that model human disease. Tbx5 and Sall4 interact both positively and negatively to finely regulate patterning and morphogenesis of the anterior forelimb and heart. Thus, a positive and negative feed-forward circuit between Tbx5 and Sall4 ensures precise patterning of embryonic limb and heart and provides a unifying mechanism for heart/hand syndromes.

Pubmed ID: 16380715

Authors

  • Koshiba-Takeuchi K
  • Takeuchi JK
  • Arruda EP
  • Kathiriya IS
  • Mo R
  • Hui CC
  • Srivastava D
  • Bruneau BG

Journal

Nature genetics

Publication Data

February 30, 2006

Associated Grants

None

Mesh Terms

  • Animals
  • Body Patterning
  • DNA-Binding Proteins
  • Extremities
  • Fibroblast Growth Factor 10
  • Forelimb
  • Gene Expression Regulation, Developmental
  • Heart
  • Heart Defects, Congenital
  • Limb Deformities, Congenital
  • Mice
  • Mutation
  • Myocardium
  • Natriuretic Peptide, C-Type
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Precursors
  • RNA, Messenger
  • T-Box Domain Proteins
  • Transcription Factors
  • Transcriptional Activation