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Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration

Gandhi, Shashank and Hutchins, Erica J. and Maruszko, Krystyna and Park, Jong H. and Thomson, Matthew and Bronner, Marianne E. (2020) Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration. eLife, 2020 (9). Art. No. e57779. ISSN 2050-084X. PMCID PMC7591248. doi:10.7554/elife.57779.

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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.

Item Type:Article
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URLURL TypeDescription CentralArticle
Gandhi, Shashank0000-0002-4081-4338
Hutchins, Erica J.0000-0002-4316-0333
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:© 2020, Gandhi et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Received: 24 April 2020; Accepted: 23 September 2020; Published: 23 September 2020. For technical assistance, we thank Fan Gao with the Caltech Bioinformatics Resource Center of the Beckman Institute, Giada Spigolon and Andres Collazo with the Caltech Biological Imaging facility of the Beckman Institute, and Sisi Chen and Paul Rivaud with the Single Cell Profiling and Engineering Center (SPEC) of the Beckman Institute. We thank members of the Bronner lab for helpful discussions. Funding: National Institutes of Health (R01DE027568) Marianne E Bronner; National Institutes of Health (R01HL14058) Marianne E Bronner; National Institutes of Health (R01DE027538) 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. Author contributions: Shashank Gandhi, Conceptualization, Resources, Software, Formal analysis, Supervision, Validation, Investigation, Visualization, Methodology, Writing - original draft, Writing - review and editing; Erica J Hutchins, Resources, Validation, Investigation, Visualization, Writing - review and editing; Krystyna Maruszko, Investigation, Visualization, Writing - original draft; Jong H Park, Matthew Thomson, Resources, Methodology; Marianne E Bronner, Conceptualization, Supervision, Funding acquisition, Writing - review and editing. Competing interests: Marianne E Bronner: Senior editor, eLife. The other authors declare that no competing interests exist. Data availability: Sequencing data files have been deposited on NCBI under the accession number PRJNA624258.
Funding AgencyGrant Number
American Heart Association18PRE34050063
Issue or Number:9
PubMed Central ID:PMC7591248
Record Number:CaltechAUTHORS:20200929-102516984
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Official Citation:Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration. eLife 2020;9: e57779; DOI: 10.7554/eLife.57779
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105631
Deposited By: Tony Diaz
Deposited On:29 Sep 2020 18:12
Last Modified:16 Nov 2021 18:44

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