Frs2α-deficiency in cardiac progenitors disrupts a subset of FGF signals required for outflow tract morphogenesis
| Autor: | Jue Zhang, Robert J. Schwartz, Yongshun Lin, Anne M. Moon, Yongsheng Lan, James F. Martin, Fen Wang, Chunhong Lin, Yongyou Zhang |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Cell signaling Mesoderm Fibroblast growth factor Epithelium Article Receptor tyrosine kinase Mice Internal medicine Morphogenesis medicine Animals Receptor Fibroblast Growth Factor Type 1 Receptor Fibroblast Growth Factor Type 2 Molecular Biology Body Patterning biology Heart development Myocardium Stem Cells Endoderm Membrane Proteins Neural crest Heart Outflow tract morphogenesis Cell biology Enzyme Activation Fibroblast Growth Factors Branchial Region Endocrinology medicine.anatomical_structure Neural Crest Mutation biology.protein Mitogen-Activated Protein Kinases Signal transduction Signal Transduction Developmental Biology |
| Zdroj: | Development. 135:3611-3622 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.025361 |
| Popis: | The cardiac outflow tract (OFT) is a developmentally complex structure derived from multiple lineages and is often defective in human congenital anomalies. Although emerging evidence shows that fibroblast growth factor(FGF) is essential for OFT development, the downstream pathways mediating FGF signaling in cardiac progenitors remain poorly understood. Here, we report that FRS2α (FRS2), an adaptor protein that links FGF receptor kinases to multiple signaling pathways, mediates crucial aspects of FGF-dependent OFT development in mouse. Ablation of Frs2α in mesodermal OFT progenitor cells that originate in the second heart field (SHF) affects their expansion into the OFT myocardium, resulting in OFT misalignment and hypoplasia. Moreover, Frs2α mutants have defective endothelial-to-mesenchymal transition and neural crest cell recruitment into the OFT cushions, resulting in OFT septation defects. These results provide new insight into the signaling molecules downstream of FGF receptor tyrosine kinases in cardiac progenitors. |
| Databáze: | OpenAIRE |
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