Sip1 mediates an E-cadherin-to-N-cadherin switch during cranial neural crest EMT
Abstract
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.
Additional Information
© 2013 Rogers et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). Submitted: 9 May 2013; Accepted: 4 November 2013; Published December 2, 2013. We would like to thank Tatjana Sauka-Spengler and the Bronner laboratory for helpful discussions. We would also like to thank the Caltech Biological Imaging center where we performed the live-imaging experiments and the Mertz Lab at the University of Wisconsin at Madison for the gift of human Zeb2 DNA. This work was supported by National Institutes of Health grant HD037105 (to M.E. Bronner) and a National Institutes of Health minority supplement P01 HD037105 (to C.D. Rogers).Attached Files
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Additional details
- PMCID
- PMC3857483
- Eprint ID
- 42918
- Resolver ID
- CaltechAUTHORS:20131210-100609180
- NIH
- HD037105
- NIH
- P01 HD037105
- Created
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2013-12-10Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field