Sip1 mediates an E-cadherin-to-N-cadherin switch during cranial neural crest EMT

• Published in: The Journal of cell biology Vol. 203; no. 5; pp. 835 - 847
• Main Authors: Rogers, Crystal D, Saxena, Ankur, Bronner, Marianne E
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 09-12-2013; The Rockefeller University Press
• Subjects: Animals; Avian Proteins - analysis; Avian Proteins - metabolism; Avian Proteins - physiology; Cancer; Chick Embryo; Epithelial-Mesenchymal Transition; Gene Knockdown Techniques; Morphology; Neural Crest - cytology; Neural Crest - metabolism; Neurulation; SMN Complex Proteins - analysis; SMN Complex Proteins - metabolism; SMN Complex Proteins - physiology; Stem cells
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201305050

The neural crest, an embryonic stem cell population, initially resides within the dorsal neural tube but subsequently undergoes an epithelial-to-mesenchymal transition (EMT) to commence migration. Although neural crest and cancer EMTs are morphologically similar, little is known regarding conservation of their underlying molecular mechanisms. We report that Sip1, which is involved in cancer EMT, plays a critical role in promoting the neural crest cell transition to a mesenchymal state. Sip1 transcripts are expressed in premigratory/migrating crest cells. After Sip1 loss, the neural crest specifier gene FoxD3 was abnormally retained in the dorsal neuroepithelium, whereas Sox10, which is normally required for emigration, was diminished. Subsequently, clumps of adherent neural crest cells remained adjacent to the neural tube and aberrantly expressed E-cadherin while lacking N-cadherin. These findings demonstrate two distinct phases of neural crest EMT, detachment and mesenchymalization, with the latter involving a novel requirement for Sip1 in regulation of cadherin expression during completion of neural crest EMT.