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.
| Item Type | Article |
|---|---|
| Keywords | Animals, Base Sequence, Bone Morphogenetic Protein Receptors, Type I/genetics, Bone Morphogenetic Proteins/*physiology, Down-Regulation/physiology, Extremities/*embryology, Heart/*embryology, Heart Defects, Congenital/genetics, Homeodomain Proteins/genetics/*physiology, Mice, Mice, Knockout, Mice, Mutant Strains, Molecular Sequence Data, Nerve Tissue Proteins/genetics/*physiology, Phenotype, Promoter Regions, Genetic, Signal Transduction/*genetics, T-Box Domain Proteins/genetics, Animals, Base Sequence, Bone Morphogenetic Protein Receptors, Type I, genetics, Bone Morphogenetic Proteins, physiology, Down-Regulation, physiology, Extremities, embryology, Heart, embryology, Heart Defects, Congenital, genetics, Homeodomain Proteins, genetics, physiology, Mice, Mice, Knockout, Mice, Mutant Strains, Molecular Sequence Data, Nerve Tissue Proteins, genetics, physiology, Phenotype, Promoter Regions, Genetic, Signal Transduction, genetics, T-Box Domain Proteins, genetics |
| ISI | 236806900016 |