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- Title
Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart.
- Authors
Koshiba-Takeuchi, Kazuko; Takeuchi, Jun K.; Arruda, Eric P.; Kathiriya, Irfan S.; Rong Mo; Chi-chung Hui; Srivastava, Deepak; Bruneau, Benoit G.
- Abstract
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.
- Subjects
GENETIC mutation; GENETICS; GENETIC transcription; GENETIC code; TRANSCRIPTION factors; PROTEINS; FORELIMB; EXTREMITIES (Anatomy); MORPHOGENESIS; SYNDROMES; DISEASES
- Publication
Nature Genetics, 2006, Vol 38, Issue 2, p175
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng1707