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RNA-binding protein Elavl1/HuR is required for maintenance of cranial neural crest specification

Hutchins, Erica J. and Gandhi, Shashank and Chacon, Jose and Piacentino, Michael and Bronner, Marianne E. (2022) RNA-binding protein Elavl1/HuR is required for maintenance of cranial neural crest specification. eLife, 11 . Art. No. e63600. ISSN 2050-084X. PMCID PMC9529247. doi:10.7554/elife.63600.

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While neural crest development is known to be transcriptionally controlled via sequential activation of gene regulatory networks (GRNs), recent evidence increasingly implicates a role for post-transcriptional regulation in modulating the output of these regulatory circuits. Using available single-cell RNA-sequencing datasets from avian embryos to identify potential post-transcriptional regulators, we found that Elavl1, which encodes for an RNA-binding protein with roles in transcript stability, was enriched in the premigratory cranial neural crest. Perturbation of Elavl1 resulted in premature neural crest delamination from the neural tube as well as significant reduction in transcripts associated with the neural crest specification GRN, phenotypes that are also observed with downregulation of the canonical Wnt inhibitor Draxin. That Draxin is the primary target for stabilization by Elavl1 during cranial neural crest specification was shown by RNA-sequencing, RNA immunoprecipitation, RNA decay measurement, and proximity ligation assays, further supporting the idea that the downregulation of neural crest specifier expression upon Elavl1 knockdown was largely due to loss of Draxin. Importantly, exogenous Draxin rescued cranial neural crest specification defects observed with Elavl1 knockdown. Thus, Elavl1 plays a critical a role in the maintenance of cranial neural crest specification via Draxin mRNA stabilization. Together, these data highlight an important intersection of post-transcriptional regulation with modulation of the neural crest specification GRN.

Item Type:Article
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URLURL TypeDescription CentralArticle ItemDiscussion Paper
Hutchins, Erica J.0000-0002-4316-0333
Gandhi, Shashank0000-0002-4081-4338
Chacon, Jose0000-0001-7965-3976
Piacentino, Michael0000-0003-1773-031X
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:© 2022, Hutchins 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. We thank A Collazo and G Spigolon for imaging assistance at the Caltech Biological Imaging Facility; M Schwarzkopf and G Shin (Molecular Technologies) for HCR probe design; I Antoshechkin of the Caltech Millard and Muriel Jacobs Genetics and Genomics Laboratory for sequencing of RNA-seq libraries; S Manohar for assistance with Axud1 3′-RACE; and G da Silva Pescador and R Galton for assistance with pilot experiments. Data availability. RNA-sequencing datasets have been deposited on NCBI under the accession number PRJNA861325. The 3' untranslated region (UTR) sequence for Axud1 has been deposited to GenBank under accession number ON920861.
Funding AgencyGrant Number
Amgen FoundationUNSPECIFIED
California State University, NorthridgeTL4GM118977
PubMed Central ID:PMC9529247
Record Number:CaltechAUTHORS:20230322-368501000.44
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:120357
Deposited By: George Porter
Deposited On:24 Mar 2023 17:23
Last Modified:24 Mar 2023 17:23

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