Hypoxia inducible factor‐2α importance for migration, proliferation, and self‐renewal of trunk neural crest cells
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.
Additional Information
© 2020 The Authors. Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association of Anatomists. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Issue Online: 01 February 2021; Version of Record online: 26 September 2020; Accepted manuscript online: 17 September 2020; Manuscript accepted: 11 September 2020; Manuscript revised: 02 September 2020; Manuscript received: 29 July 2020. The authors would like to thank Erica Hutchins, Shashank Gandhi, and Siv Beckman for skillful technical assistance, Felipe Vieceli for providing templates for in situ hybridization probes and Anni Glud and Ronnie N. Glud for providing microsensor technique and expertise. The authors thank Center for Translational Genomics, Lund University, and Clinical Genomics Lund, SciLifeLab for providing sequencing service. Support by NBIS (National Bioinformatics Infrastructure Sweden) is gratefully acknowledged. This work was supported by the Swedish Cancer Society, the Swedish Childhood Cancer Fund, the Crafoord Foundation, Jeansson Foundations, Ollie and Elof Ericsson's Foundation, the Mary Bevé Foundation, Magnus Bergvall's Foundation, the Thelma Zoéga Foundation for medical research, Hans von Kantzow's Foundation, the Royal Physiographic Society of Lund, the Gyllenstierna Krapperup's Foundation, and Gunnar Nilssons Cancerstiftelse (to S. M.), DE027568 and R01HL14058 (to M. E. B.). The authors declare no conflict of interests. Author Contributions: Camilla U. Niklasson: Investigation, writing‐review and editing. Elina Fredlund: Investigation, writing‐review and editing. Emanuela Monni: Resources, writing‐review and editing. Jessica M. Lindvall: Data curation, formal analysis, software, writing‐review and editing. Zaal Kokaia: Resources, writing‐review and editing. Emma U. Hammarlund: Formal analysis, investigation, methodology, validation, visualization, writing‐review and editing. Marianne E. Bronner: Conceptualization, funding acquisition, methodology, supervision, writing‐review and editing. Sofie Mohlin: Conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, supervision, validation, visualization, writing‐original draft, writing‐review and editing.Attached Files
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Additional details
- Alternative title
- HIF-2α importance for migration, proliferation and self‐renewal of trunk neural crest cells
- Eprint ID
- 105484
- Resolver ID
- CaltechAUTHORS:20200923-074659440
- National Bioinformatics Infrastructure Sweden
- Swedish Cancer Society
- Swedish Childhood Cancer Fund
- Crafoord Foundation
- Jeansson Foundations
- Ollie and Elof Ericsson's Foundation
- Mary Bevé Foundation
- Magnus Bergvall's Foundation
- Thelma Zoéga Foundation
- Hans von Kantzow's Foundation
- Royal Physiographic Society of Lund
- Gyllenstierna Krapperup's Foundation
- Gunnar Nilssons Cancerstiftelse
- NIH
- DE027568
- NIH
- R01HL14058
- Created
-
2020-09-23Created from EPrint's datestamp field
- Updated
-
2021-11-16Created from EPrint's last_modified field
- Caltech groups
- Division of Biology and Biological Engineering