Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration
- California Institute of Technology, United States
Abstract
During gastrulation, neural crest cells are specified at the neural plate border, as characterized by Pax7 expression. Using single-cell RNA sequencing coupled with high resolution in situ hybridization to identify novel transcriptional regulators, we show that chromatin remodeler Hmga1 is highly expressed prior to specification and maintained in migrating chick neural crest cells. Temporally-controlled CRISPR-Cas9-mediated knockouts uncovered two distinct functions of Hmga1 in neural crest development. At the neural plate border, Hmga1 regulates Pax7-dependent neural crest lineage specification. At premigratory stages, a second role manifests where Hmga1 loss reduces cranial crest emigration from the dorsal neural tube independent of Pax7. Interestingly, this is rescued by stabilized ß-catenin, thus implicating Hmga1 as a canonical Wnt activator. Together, our results show that Hmga1 functions in a bimodal manner during neural crest development to regulate specification at the neural plate border, and subsequent emigration from the neural tube via canonical Wnt signaling.
Data availability
Sequencing data files have been deposited on NCBI under the accession number PRJNA624258.
Article and author information
Author details
Marianne E Bronner
Funding
National Institutes of Health (R01DE027568)
- Marianne E Bronner
National Institutes of Health (R01HL14058)
- Marianne E Bronner
American Heart Association (18PRE34050063)
- Shashank Gandhi
National Institutes of Health (K99DE028592)
- Erica J Hutchins
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Lukas Sommer, University of Zurich, Switzerland
Version history
- Received: April 24, 2020
- Accepted: September 23, 2020
- Accepted Manuscript published: September 23, 2020 (version 1)
- Version of Record published: October 27, 2020 (version 2)
Copyright
© 2020, Gandhi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration
eLife 9:e57779.
https://doi.org/10.7554/eLife.57779
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