title: Neural crest cell-autonomous roles of fibronectin in cardiovascular development.
abstract: The chemical and mechanical properties of extracellular matrices (ECMs) modulate diverse aspects of cellular fates; however, how regional heterogeneity in ECM composition regulates developmental programs is not well understood. We discovered that fibronectin 1 (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 morphogenesis of the aortic arch artery and differentiation of NC cells into vascular smooth muscle cells (VSMCs) by regulating Notch signaling. We show that NC Fn1 signals in an NC cell-autonomous manner through integrin α5β1 expressed by the NC, leading to activation of Notch and differentiation of VSMCs. Our data demonstrate an essential role of the localized synthesis of Fn1 in cardiovascular development and spatial regulation of Notch signaling.
authors.affiliation: Sidney Kimmel Medical College of Thomas Jefferson University, Department of Medicine, Center for Translational Medicine, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Sidney Kimmel Medical College of Thomas Jefferson University, Department of Medicine, Center for Translational Medicine, 1020 Locust Street, Philadelphia, PA 19107, USA sophie.astrof@gmail.com.
authors.forename: Sophie
authors.initials: S
authors.lastname: Astrof
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000196:embryology*; D002454:Cell Differentiation / Q000502:physiology; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009432:Neural Crest / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1; D051880:Receptors, Notch
keywords: Cardiovascular development; Fibronectin; Integrin α5β1; Lateral induction; Neural crest; Notch; Vascular smooth muscle cells