Fibronectin signals through integrin α5β1 to regulate cardiovascular development in a cell type-specific manner.

摘要: Fibronectin (Fn1) is an evolutionarily conserved extracellular matrix glycoprotein essential for embryonic development. Global deletion of Fn1 leads to mid-gestation lethality from cardiovascular defects. However, severe morphogenetic defects that occur early in embryogenesis these embryos precluded assigning a direct role We noticed expressed strikingly non-uniform patterns during mouse embryogenesis, and its expression particularly enriched the pharyngeal region corresponding with arches 3, 4, 6. This bears special importance developing system, we hypothesized localized enrichment may be morphogenesis. To test this hypothesis, ablated using Isl1Cre knock-in strain mice. Deletion resulted defective formation 4th arch arteries (PAAs), aberrant development cardiac outflow tract (OFT), ventricular septum determine cell types responding signaling development, deleted major receptor, integrin α5 strain, observed same spectrum abnormalities seen conditional mutants. Additional mutagenesis studies designed ablate distinct within Isl1+ tissues their derivatives, suggested mesoderm, endothelium, surface ectoderm neural crest were not required PAA formation. Our suggest (as yet unknown) α5-dependent signal extrinsic endothelium mediates PAAs.