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PMID:16556916
| Citation |
Yang, L, Cai, CL, Lin, L, Qyang, Y, Chung, C, Monteiro, RM, Mummery, CL, Fishman, GI, Cogen, A and Evans, S (2006) Isl1Cre reveals a common Bmp pathway in heart and limb development. Development 133:1575-85 |
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| Abstract |
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. |
| Links |
PubMed Online version:10.1242/dev.02322 |
| 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; Homeodomain Proteins/physiology; LIM-Homeodomain Proteins; Mice; Mice, Knockout; Mice, Mutant Strains; Molecular Sequence Data; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/physiology; Phenotype; Promoter Regions, Genetic; Signal Transduction/genetics; T-Box Domain Proteins/genetics; Transcription Factors |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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