title: p53 coordinates cranial neural crest cell growth and epithelial-mesenchymal transition/delamination processes.
abstract: Neural crest development involves epithelial-mesenchymal transition (EMT), during which epithelial cells are converted into individual migratory cells. Notably, the same signaling pathways regulate EMT function during both development and tumor metastasis. p53 plays multiple roles in the prevention of tumor development; however, its precise roles during embryogenesis are less clear. We have investigated the role of p53 in early cranial neural crest (CNC) development in chick and mouse embryos. In the mouse, p53 knockout embryos displayed broad craniofacial defects in skeletal, neuronal and muscle tissues. In the chick, p53 is expressed in CNC progenitors and its expression decreases with their delamination from the neural tube. Stabilization of p53 protein using a pharmacological inhibitor of its negative regulator, MDM2, resulted in reduced SNAIL2 (SLUG) and ETS1 expression, fewer migrating CNC cells and in craniofacial defects. By contrast, electroporation of a dominant-negative p53 construct increased PAX7(+) SOX9(+) CNC progenitors and EMT/delamination of CNC from the neural tube, although the migration of these cells to the periphery was impaired. Investigating the underlying molecular mechanisms revealed that p53 coordinates CNC cell growth and EMT/delamination processes by affecting cell cycle gene expression and proliferation at discrete developmental stages; disruption of these processes can lead to craniofacial defects.
authors: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Ariel
authors: A
authors: Rinon
authors: Alina
authors: A
authors: Molchadsky
authors: Elisha
authors: E
authors: Nathan
authors: Gili
authors: G
authors: Yovel
authors: Varda
authors: V
authors: Rotter
authors: Rachel
authors: R
authors: Sarig
authors: Eldad
authors: E
authors: Tzahor
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D019465:Craniofacial Abnormalities / Q000150:complications / Q000196:embryology / Q000235:genetics / Q000473:pathology; D004622:Embryo, Mammalian; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics* / Q000502:physiology; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009139:Musculoskeletal Abnormalities / Q000150:complications / Q000196:embryology / Q000235:genetics / Q000473:pathology; D009432:Neural Crest / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D012886:Skull / Q000196:embryology* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D007797:Laminin; D016159:Tumor Suppressor Protein p53