Hypoxia inducible factor-2α importance for migration, proliferation, and self-renewal of trunk neural crest cells

Research output: Contribution to journalArticle

Abstract

Background: The neural crest is a transient embryonic stem cell population. Hypoxia inducible factor (HIF)-2α is associated with neural crest stem cell appearance and aggressiveness in tumors. However, little is known about its role in normal neural crest development. Results: Here, we show that HIF-2α is expressed in trunk neural crest cells of human, murine, and avian embryos. Knockdown as well as overexpression of HIF-2α in vivo causes developmental delays, induces proliferation, and self-renewal capacity of neural crest cells while decreasing the proportion of neural crest cells that migrate ventrally to sympathoadrenal sites. Reflecting the in vivo phenotype, transcriptome changes after loss of HIF-2α reveal enrichment of genes associated with cancer, invasion, epithelial-to-mesenchymal transition, and growth arrest. Conclusions: Taken together, these results suggest that expression levels of HIF-2α must be strictly controlled during normal trunk neural crest development and that dysregulated levels affects several important features connected to stemness, migration, and development.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
  • Stockholm University
  • California Institute of Technology
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • embryogenesis, HIF-2α, migration, neural crest, stem cells, trunk neural crest
Original languageEnglish
Pages (from-to)191-236
JournalDevelopmental Dynamics
Volume250
Issue number2
Publication statusPublished - 2021
Publication categoryResearch
Peer-reviewedYes