The hypoxia factor Hif-1alpha controls neural crest chemotaxis and epithelial to mesenchymal transition
- Authors
- Barriga, E.H., Maxwell, P.H., Reyes, A.E., and Mayor, R.
- ID
- ZDB-PUB-130708-3
- Date
- 2013
- Source
- The Journal of cell biology 201(5): 759-776 (Journal)
- Registered Authors
- Mayor, Roberto
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Hypoxia
- Chemotaxis/genetics*
- Embryo, Nonmammalian/cytology
- Embryonic Development/genetics
- Epithelial-Mesenchymal Transition/genetics*
- Gene Expression Regulation, Developmental
- Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
- Hypoxia-Inducible Factor 1, alpha Subunit/physiology*
- Neural Crest/cytology*
- Neural Crest/metabolism
- Receptors, CXCR4/genetics
- Twist-Related Protein 1/genetics
- Xenopus laevis
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 23712262 Full text @ J. Cell Biol.
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.