Isl1Cre reveals a common Bmp pathway in heart and limb development
Copyright policy )Isl1Cre reveals a common Bmp pathway in heart and limb development
A number of human congenital disorders present with both heart and limb defects, consistent with common genetic pathways. We have recently shown that the LIM homeodomain transcription factor islet 1 (Isl1) marks a subset of cardiac progenitors. Here, we perform lineage studies with an Isl1Cre mouse line to demonstrate that Isl1 also marks a subset of limb progenitors. In both cardiac and limb progenitors, Isl1 expression is downregulated as progenitors migrate in to form either heart or limb. To investigate common heart-limb pathways in Isl1-expressing progenitors, we ablated the Type I Bmp receptor,Bmpr1a utilizing Isl1Cre/+. Analysis of consequent heart and limb phenotypes has revealed novel requirements for Bmp signaling. Additionally, we find that Bmp signaling in Isl1-expressing progenitors is required for expression of T-box transcription factors Tbx2 and Tbx3 in heart and limb. Tbx3 is required for heart and limb formation, and is mutated in ulnar-mammary syndrome. We provide evidence that the Tbx3 promoter is directly regulated by Bmp Smads in vivo.
- University of California, San Diego United States
- Harvard University United States
- University of California, San Diego United States
- Massachusetts General Hospital United States
- New York University United States
Heart Defects, Congenital, Homeodomain Proteins, Mice, Knockout, Base Sequence, LIM-Homeodomain Proteins, Molecular Sequence Data, Down-Regulation, Extremities, Heart, Nerve Tissue Proteins, Mice, Mutant Strains, Mice, Phenotype, Bone Morphogenetic Proteins, Animals, Promoter Regions, Genetic, T-Box Domain Proteins, Bone Morphogenetic Protein Receptors, Type I, Signal Transduction, Transcription Factors
Heart Defects, Congenital, Homeodomain Proteins, Mice, Knockout, Base Sequence, LIM-Homeodomain Proteins, Molecular Sequence Data, Down-Regulation, Extremities, Heart, Nerve Tissue Proteins, Mice, Mutant Strains, Mice, Phenotype, Bone Morphogenetic Proteins, Animals, Promoter Regions, Genetic, T-Box Domain Proteins, Bone Morphogenetic Protein Receptors, Type I, Signal Transduction, Transcription Factors
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