HIF‐2α importance for migration, proliferation and self‐renewal of trunk neural crest cells

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. This article is protected by copyright. All rights reserved.