title: Mesodermal expression of integrin α5β1 regulates neural crest development and cardiovascular morphogenesis.
abstract: Integrin α5-null embryos die in mid-gestation from severe defects in cardiovascular morphogenesis, which stem from defective development of the neural crest, heart and vasculature. To investigate the role of integrin α5β1 in cardiovascular development, we used the Mesp1(Cre) knock-in strain of mice to ablate integrin α5 in the anterior mesoderm, which gives rise to all of the cardiac and many of the vascular and muscle lineages in the anterior portion of the embryo. Surprisingly, we found that mutant embryos displayed numerous defects related to the abnormal development of the neural crest such as cleft palate, ventricular septal defect, abnormal development of hypoglossal nerves, and defective remodeling of the aortic arch arteries. We found that defects in arch artery remodeling stem from the role of mesodermal integrin α5β1 in neural crest proliferation and differentiation into vascular smooth muscle cells, while proliferation of pharyngeal mesoderm and differentiation of mesodermal derivatives into vascular smooth muscle cells was not defective. Taken together our studies demonstrate a requisite role for mesodermal integrin α5β1 in signaling between the mesoderm and the neural crest, thereby regulating neural crest-dependent morphogenesis of essential embryonic structures.
authors.affiliation: Thomas Jefferson University, Department of Medicine, Center for Translational Medicine, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
authors.affiliation: 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: Thomas Jefferson University, Department of Medicine, Center for Translational Medicine, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Mittal
authors.affiliation: Thomas Jefferson University, Department of Medicine, Center for Translational Medicine, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Sonam
authors.initials: S
authors.lastname: Dhiman
authors.affiliation: Thomas Jefferson University, Department of Medicine, Center for Translational Medicine, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Shuan-Yu
authors.initials: SY
authors.lastname: Hou
authors.affiliation: Childrens Hospital of Pennsylvania, University of Pennsylvania, Philadelphia, PA 19107, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Degenhardt
authors.affiliation: Thomas Jefferson University, Department of Medicine, Center for Translational Medicine, 1020 Locust Street, Philadelphia, PA 19107, USA. Electronic address: sophie.astrof@gmail.com.
authors.forename: Sophie
authors.initials: S
authors.lastname: Astrof
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000196:embryology; D002319:Cardiovascular System / Q000196:embryology*; D002454:Cell Differentiation / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D008648:Mesoderm / Q000196:embryology*; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology*; D009432:Neural Crest / Q000196:embryology*
chemical_list: D017931:DNA Primers; D039081:Integrin alpha5beta1
keywords: Aortic arch artery development; Integrin alpha5; Mesoderm; Neural crest