Epigenetic inactivation of miR-203 as a key step in neural crest epithelial-to-mesenchymal transition.
Sanchez-Vasquez, E., Bronner, M. E. and Strobl-Mazzulla, P. H.
Laboratory of Developmental Biology, Instituto Tecnologico de Chascomus (CONICET-UNSAM), Chascomus 7130, Argentina.
Division of Biology 139-74, California Institute of Technology, Pasadena, CA 91125, USA.
Laboratory of Developmental Biology, Instituto Tecnologico de Chascomus (CONICET-UNSAM), Chascomus 7130, Argentina strobl@intech.gov.ar.
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.
Development 146(7): (2019)