Format

Send to

Choose Destination
Development. 2019 Apr 11;146(7). pii: dev171017. doi: 10.1242/dev.171017.

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

Author information

1
Laboratory of Developmental Biology, Instituto Tecnológico de Chascomús (CONICET-UNSAM), Chascomús 7130, Argentina.
2
Division of Biology 139-74, California Institute of Technology, Pasadena, CA 91125, USA.
3
Laboratory of Developmental Biology, Instituto Tecnológico de Chascomús (CONICET-UNSAM), Chascomús 7130, Argentina strobl@intech.gov.ar.

Abstract

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.

KEYWORDS:

DNA methylation; EMT; Migration; Neural crest; Phf12; Snail2; miR-203

PMID:
30910825
PMCID:
PMC6467475
[Available on 2020-04-01]
DOI:
10.1242/dev.171017

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center