Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Abstract

The chemical and mechanical properties of extracellular matrices (ECM) modulate diverse aspects of cellular fates; however, how regional heterogeneity in the ECM composition regulates developmental programs is not well understood. We discovered that Fn1 is expressed in strikingly non-uniform patterns during mouse development, suggesting that regionalized synthesis of the ECM plays cell-specific regulatory roles during embryogenesis. To test this hypothesis, we ablated Fn1 in the neural crest (NC), a population of multi-potent progenitors expressing high levels of Fn1. We found that Fn1 synthesized by the NC mediated aortic arch artery morphogenesis and the differentiation of NC cells into vascular smooth muscle cells (VSMCs) by regulating Notch signaling. We demonstrate that NC Fn1 signals in neural crest cell-autonomous manner through integrin α5β1 expressed by the NC leading to the activation of Notch and the differentiation of VSMCs. Our data demonstrate an essential role of the localized synthesis of Fn1 in cardiovascular development and spatial regulation of Notch signaling.