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

First Author  Niklasson CU Year  2021
Journal  Dev Dyn Volume  250
Issue  2 Pages  191-236
PubMed ID  32940375 Mgi Jnum  J:302179
Mgi Id  MGI:6506314 Doi  10.1002/dvdy.253
Citation  Niklasson CU, et al. (2021) Hypoxia inducible factor-2alpha importance for migration, proliferation, and self-renewal of trunk neural crest cells. Dev Dyn 250(2):191-236
abstractText  BACKGROUND: The neural crest is a transient embryonic stem cell population. Hypoxia inducible factor (HIF)-2alpha 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-2alpha is expressed in trunk neural crest cells of human, murine, and avian embryos. Knockdown as well as overexpression of HIF-2alpha 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-2alpha 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-2alpha must be strictly controlled during normal trunk neural crest development and that dysregulated levels affects several important features connected to stemness, migration, and development.
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