title: Notch signal reception is required in vascular smooth muscle cells for ductus arteriosus closure.
abstract: The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus, and is one of the most common congenital heart defects. Our previous work demonstrated that vascular smooth muscle cell expression of the Jag1 gene, which encodes a ligand for Notch family receptors, is essential for postnatal closure of the ductus arteriosus in mice. However, it was not known what cell population was responsible for receiving the Jag1-mediated signal. Here we show, using smooth muscle cell-specific deletion of the Rbpj gene, which encodes a transcription factor that mediates all canonical Notch signaling, that Notch signal reception in the vascular smooth muscle cell compartment is required for ductus arteriosus closure. These data indicate that homotypic vascular smooth muscle cell interactions are required for proper contractile smooth muscle cell differentiation and postnatal closure of the ductus arteriosus in mice.
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, 04074.
authors.forename: Luke T
authors.initials: LT
authors.lastname: Krebs
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, 04074.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Norton
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, 04074.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gridley
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004373:Ductus Arteriosus / Q000196:embryology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins
keywords: birth defects; lateral induction; vascular smooth muscle