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Epigenetic inactivation of miR-203 as a key step in neural crest epithelial-to-mesenchymal transition

Sánchez-Vásquez, Estefania and Bronner, Marianne E. and Strobl-Mazzulla, Pablo H. (2019) Epigenetic inactivation of miR-203 as a key step in neural crest epithelial-to-mesenchymal transition. Development, 146 (7). Art. No. dev171017. ISSN 0950-1991. PMCID PMC6467475. doi:10.1242/dev.171017.

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miR-203 is a tumor-suppressor microRNA with known functions in cancer metastasis. Here, we explore its normal developmental role in the context of neural crest development. During the epithelial-to-mesenchymal transition of neural crest cells to emigrate from the neural tube, miR-203 displays a reciprocal expression pattern with key regulators of neural crest delamination, Phf12 and Snail2, and interacts with their 3′UTRs. We show that ectopic maintenance of miR-203 inhibits neural crest migration in chick, whereas its functional inhibition using a ‘sponge’ vector or morpholinos promotes premature neural crest delamination. Bisulfite sequencing further shows that epigenetic repression of miR-203 is mediated by the de novo DNA methyltransferase DNMT3B, the recruitment of which to regulatory regions on the miR-203 locus is directed by SNAIL2 in a negative-feedback loop. These findings reveal an important role for miR-203 in an epigenetic-microRNA regulatory network that influences the timing of neural crest delamination.

Item Type:Article
Related URLs:
URLURL TypeDescription Paper CentralArticle
Bronner, Marianne E.0000-0003-4274-1862
Strobl-Mazzulla, Pablo H.0000-0003-0591-6168
Additional Information:© 2019 Published by The Company of Biologists Ltd. Received August 14, 2018; Accepted March 15, 2019; Published 25 March 2019. We thank Dr Xinwei Cao for the two-colored sensor vector and Dr Andrew Pollok for advice on the design of sponge vector. We also thank the Wood-Whelan research fellowships and The Company of Biologists (Development Travelling Fellowship DEV-180502) for travel support for E.S.-V. The authors declare no competing or financial interests. Author contributions: Conceptualization: P.H.S.-M.; Methodology: E.S.-V., P.H.S.-M.; Validation: E.S.-V.; Formal analysis: E.S.-V.; Investigation: E.S.-V., P.H.S.-M.; Resources: M.E.B., P.H.S.-M.; Writing - original draft: E.S.-V., P.H.S.-M.; Writing - review & editing: M.E.B., P.H.S.-M.; Visualization: E.S.-V., P.H.S.-M.; Supervision: M.E.B., P.H.S.-M.; Project administration: P.H.S.-M.; Funding acquisition: M.E.B., P.H.S.-M. This work was supported by the Fogarty International Center of the National Institutes of Health (R21TW011224 to M.E.B. and P.H.S.-M.) and by the Agencia Nacional de Promoción Científica y Tecnológica (PICT 2016-0747 to P.H.S.-M.). Deposited in PMC for release after 12 months.
Funding AgencyGrant Number
Agencia Nacional de Promoción Científica y TecnológicaPICT 2016-0747
Wood-Whelan Research FellowshipUNSPECIFIED
Company of BiologistsDEV-180502
Subject Keywords:EMT, neural crest, miR-203, Snail2, DNA methylation, Phf12, migration
Issue or Number:7
PubMed Central ID:PMC6467475
Record Number:CaltechAUTHORS:20180927-114223566
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Official Citation:Epigenetic inactivation of miR-203 as a key step in neural crest epithelial-to-mesenchymal transition Estefanía Sánchez-Vásquez, Marianne E. Bronner, Pablo H. Strobl-Mazzulla Development 2019 146: dev171017 doi: 10.1242/dev.171017 Published 11 April 2019
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:89998
Deposited By: George Porter
Deposited On:28 Sep 2018 15:23
Last Modified:15 Feb 2022 23:42

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