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

Hutchins, Erica J. and Chacon, Jose and Bronner, Marianne E. (2020) RNA-binding protein Elavl1/HuR is required for maintenance of cranial neural crest specification. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20201015-152733431

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Abstract

Neural crest development is 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 RNA-sequencing data from avian embryos to identify potential post-transcriptional regulators, we observed enrichment during early neural crest development of Elavl1, which encodes for the RNA-binding protein HuR. Immunohistochemical analyses revealed expression of HuR following establishment of the neural plate border. Perturbation of HuR resulted in premature neural crest delamination from the neural tube as well as significant reduction in transcripts associated with the neural crest specification GRN (Axud1 and FoxD3), phenotypes also observed with downregulation of the canonical Wnt inhibitor Draxin. RNA pulldown further shows that Draxin is a specific target of HuR. Importantly, overexpression of exogenous Draxin was able to rescue the cranial neural crest specification defects observed with HuR knockdown. Thus, HuR plays a critical a role in the maintenance of cranial neural crest specification, at least partially 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:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.10.14.338715DOIDiscussion Paper
ORCID:
AuthorORCID
Hutchins, Erica J.0000-0002-4316-0333
Chacon, Jose0000-0001-7965-3976
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. 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; G. da Silva Pescador and R. Galton for assistance with pilot experiments. This work was supported by the National Institutes of Health [R01DE027538 and R01DE027568 to M.E.B; K99DE028592 to E.J.H], the Amgen Foundation Caltech Amgen Scholars Program [J.C.], and the California State University—Northridge BUILD POD ER program [J.C.]. The authors have declared no competing interest.
Funders:
Funding AgencyGrant Number
NIHR01DE027538
NIHR01DE027568
NIHK99DE028592
Amgen Scholars ProgramUNSPECIFIED
California State University, NorthridgeUNSPECIFIED
Record Number:CaltechAUTHORS:20201015-152733431
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201015-152733431
Official Citation:RNA-binding protein Elavl1/HuR is required for maintenance of cranial neural crest specification Erica J Hutchins, Jose Chacon, Marianne E. Bronner bioRxiv 2020.10.14.338715; doi: https://doi.org/10.1101/2020.10.14.338715
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106093
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:16 Oct 2020 14:41
Last Modified:16 Oct 2020 14:41

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