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

Niklasson, Camilla U. LU ; Fredlund, Elina LU ; Monni, Emanuela LU ; Lindvall, Jessica M. ; Kokaia, Zaal LU orcid ; Hammarlund, Emma U. LU ; Bronner, Marianne E. and Mohlin, Sofie LU orcid (2021) In Developmental Dynamics 250(2). p.191-236
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... (More)

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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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
embryogenesis, HIF-2α, migration, neural crest, stem cells, trunk neural crest
in
Developmental Dynamics
volume
250
issue
2
pages
191 - 236
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85091426123
  • pmid:32940375
ISSN
1058-8388
DOI
10.1002/dvdy.253
language
English
LU publication?
yes
id
7c2b8dff-966d-468c-868d-55bbe6462e50
date added to LUP
2020-10-28 08:14:13
date last changed
2024-07-10 23:59:59
@article{7c2b8dff-966d-468c-868d-55bbe6462e50,
  abstract     = {{<p>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.</p>}},
  author       = {{Niklasson, Camilla U. and Fredlund, Elina and Monni, Emanuela and Lindvall, Jessica M. and Kokaia, Zaal and Hammarlund, Emma U. and Bronner, Marianne E. and Mohlin, Sofie}},
  issn         = {{1058-8388}},
  keywords     = {{embryogenesis; HIF-2α; migration; neural crest; stem cells; trunk neural crest}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{191--236}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Developmental Dynamics}},
  title        = {{Hypoxia inducible factor-2α importance for migration, proliferation, and self-renewal of trunk neural crest cells}},
  url          = {{http://dx.doi.org/10.1002/dvdy.253}},
  doi          = {{10.1002/dvdy.253}},
  volume       = {{250}},
  year         = {{2021}},
}