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

Kazuko Koshiba-Takeuchi; Jun K Takeuchi; Eric P Arruda; Irfan S Kathiriya; Rong Mo; Chi-chung Hui; Deepak Srivastava; Benoit G Bruneau

doi:10.1038/ng1707

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

Nat Genet. 2006 Feb;38(2):175-83. doi: 10.1038/ng1707. Epub 2005 Dec 25.

Authors

Kazuko Koshiba-Takeuchi¹, Jun K Takeuchi, Eric P Arruda, Irfan S Kathiriya, Rong Mo, Chi-chung Hui, Deepak Srivastava, Benoit G Bruneau

Affiliation

¹ Programs in Cardiovascular Research, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.

PMID: 16380715
DOI: 10.1038/ng1707

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

DNA-Binding Proteins
Fgf10 protein, mouse
Fibroblast Growth Factor 10
Nppa protein, mouse
Protein Precursors
RNA, Messenger
Sall4 protein, mouse
T-Box Domain Proteins
T-box transcription factor 5
Tbx4 protein, mouse
Transcription Factors
Natriuretic Peptide, C-Type
Atrial Natriuretic Factor