title: α5 and αv integrins cooperate to regulate vascular smooth muscle and neural crest functions in vivo.
abstract: The RGD-binding α5 and αv integrins have been shown to be key regulators of vascular smooth muscle cell (vSMC) function in vitro. However, their role on vSMCs during vascular development in vivo remains unclear. To address this issue, we have generated mice that lack α5, αv or both α5 and αv integrins on their vSMCs, using the SM22α-Cre transgenic mouse line. To our surprise, neither α5 nor αv mutants displayed any obvious vascular defects during embryonic development. By contrast, mice lacking both α5 and αv integrins developed interrupted aortic arches, large brachiocephalic/carotid artery aneurysms and cardiac septation defects, but developed extensive and apparently normal vasculature in the skin. Cardiovascular defects were also found, along with cleft palates and ectopically located thymi, in Wnt1-Cre α5/αv mutants, suggesting that α5 and αv cooperate on neural crest-derived cells to control the remodelling of the pharyngeal arches and the septation of the heart and outflow tract. Analysis of cultured α5/αv-deficient vSMCs suggests that this is achieved, at least in part, through proper assembly of RGD-containing extracellular matrix proteins and the correct incorporation and activation of latent TGF-β.
authors: Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Christopher J
authors: CJ
authors: Turner
authors: Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Kwabena
authors: K
authors: Badu-Nkansah
authors: Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Denise
authors: D
authors: Crowley
authors: Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Arjan
authors: A
authors: van der Flier
authors: Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA rohynes@mit.edu.
authors: Richard O
authors: RO
authors: Hynes
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D005260:Female; D006321:Heart / Q000196:embryology; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism*; D039564:Integrin alphaV / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism*
chemical_list: D039482:Integrin alpha5; D039564:Integrin alphaV
keywords: Aneurysms; Blood vessels; Cardiovascular development; Integrin; Neural crest; Vascular smooth muscle cells