Hypoxia inducible factor-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)-2 alpha 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-2 alpha is expressed in trunk neural crest cells of human, murine, and avian embryos. Knockdown as well as overexpression of HIF-2 alpha 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-2 alpha 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-2 alpha must be strictly controlled during normal trunk neural crest development and that dysregulated levels affects several important features connected to stemness, migration, and development.

Automated summary

HIF-2α plays a crucial role in normal trunk neural crest development, with dysregulation affecting important features such as stemness, migration, and development. Its expression levels must be strictly controlled to ensure proper neural crest cell functions.