title: The hypoxia factor Hif-1α 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-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.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, England, UK.
authors.forename: Elias H
authors.initials: EH
authors.lastname: Barriga
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Maxwell
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Reyes
authors.forename: Roberto
authors.initials: R
authors.lastname: Mayor
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002633:Chemotaxis / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000166:cytology; D047108:Embryonic Development / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000235:genetics; D014982:Xenopus laevis; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019718:Receptors, CXCR4; D051879:Twist-Related Protein 1