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

ABSTRACT: 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-1? 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-1? by antisense morpholinos in Xenopus laevis or zebrafish embryos led to complete inhibition of neural crest migration. We show that Hif-1? controls the expression of Twist, which in turn represses E-cadherin during epithelial to mesenchymal transition (EMT) of neural crest cells. Thus, Hif-1? allows cells to initiate migration by promoting the release of cell-cell adhesions. Additionally, Hif-1? controls chemotaxis toward the chemokine SDF-1 by regulating expression of its receptor Cxcr4. Our results point to Hif-1? as a novel and key regulator that integrates EMT and chemotaxis during migration of neural crest cells.

SUBMITTER: Barriga EH 

PROVIDER: S-EPMC3664719 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature