Hypoxia Inducible Factor-2α Importance for Migration, Proliferation, and Self-renewal of Trunk Neural Crest Cells

Overview

Journal Dev Dyn

Publisher Wiley

Specialty Anatomy & Histology

Date 2020 Sep 17

PMID 32940375

Citations 14

Authors

Camilla U Niklasson

Elina Fredlund

Emanuela Monni

Jessica M Lindvall

Zaal Kokaia

Emma U Hammarlund

Marianne E Bronner

Sofie Mohlin

Affiliations

Soon will be listed here.

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.

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