title: Defective ALK5 signaling in the neural crest leads to increased postmigratory neural crest cell apoptosis and severe outflow tract defects.
abstract: BACKGROUND
  Congenital cardiovascular diseases are the most common form of birth defects in humans. A substantial portion of these defects has been associated with inappropriate induction, migration, differentiation and patterning of pluripotent cardiac neural crest stem cells. While TGF-beta-superfamily signaling has been strongly implicated in neural crest cell development, the detailed molecular signaling mechanisms in vivo are still poorly understood.
  
  
  RESULTS
  We deleted the TGF-beta type I receptor Alk5 specifically in the mouse neural crest cell lineage. Failure in signaling via ALK5 leads to severe cardiovascular and pharyngeal defects, including inappropriate remodeling of pharyngeal arch arteries, abnormal aortic sac development, failure in pharyngeal organ migration and persistent truncus arteriosus. While ALK5 is not required for neural crest cell migration, our results demonstrate that it plays an important role in the survival of post-migratory cardiac neural crest cells.
  
  
  CONCLUSIONS
  Our results demonstrate that ALK5-mediated signaling in neural crest cells plays an essential cell-autonomous role in the pharyngeal and cardiac outflow tract development.
authors.affiliation: Developmental Biology Program, The Saban Research Institute of Childrens Hospital Los Angeles, Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA. jikwang@chla.usc.edu
authors.forename: Jikui
authors.initials: J
authors.lastname: Wang
authors.forename: Andre
authors.initials: A
authors.lastname: Nagy
authors.forename: Jonas
authors.initials: J
authors.lastname: Larsson
authors.forename: Marek
authors.initials: M
authors.lastname: Dudas
authors.forename: Henry M
authors.initials: HM
authors.lastname: Sucov
authors.forename: Vesa
authors.initials: V
authors.lastname: Kaartinen
mesh_terms: D030201:Activin Receptors, Type I / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000002:abnormalities / Q000196:embryology; D017209:Apoptosis / Q000235:genetics*; D001934:Branchial Region / Q000002:abnormalities / Q000196:embryology; D002465:Cell Movement / Q000235:genetics*; D005260:Female; D006330:Heart Defects, Congenital / Q000196:embryology / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009432:Neural Crest / Q000196:embryology* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse