The hypoxia factor Hif-1α controls neural crest chemotaxis and epithelial to mesenchymal transition

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Miniatura
Fecha
2013-05
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
Rockefeller University Press
Nombre de Curso
Licencia CC
Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)
Licencia CC
https://rupress.org/pages/permissions-and-licensing
Resumen
One of the most important mechanisms that promotes metastasis is the stabilization of Hif-1 (hypoxia-inducible transcription factor 1). We decided to test whether Hif-1α also was required for early embryonic development. We focused our attention on the development of the neural crest, a highly migratory embryonic cell population whose behavior has been likened to cancer metastasis. Inhibition of Hif-1α by antisense morpholinos in Xenopus laevis or zebrafish embryos led to complete inhibition of neural crest migration. We show that Hif-1α controls the expression of Twist, which in turn represses E-cadherin during epithelial to mesenchymal transition (EMT) of neural crest cells. Thus, Hif-1α allows cells to initiate migration by promoting the release of cell- cell adhesions. Additionally, Hif-1α controls chemotaxis toward the chemokine SDF-1 by regulating expression of its receptor Cxcr4. Our results point to Hif-1α as a novel and key regulator that integrates EMT and chemotaxis during migration of neural crest cells.
Notas
Indexación: Scopus.
Palabras clave
Neural Crest, Neuroectoderm, Animals
Citación
Journal of Cell Biology, Volume 201, Issue 5, Pages 759 - 776, May 2013
DOI
10.1083/jcb.201212100
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