Premium
MiR‐23b and miR‐199a impair epithelial‐to‐mesenchymal transition during atrioventricular endocardial cushion formation
Author(s) -
Bonet Fernando,
Dueñas Ángel,
LópezSánchez Carmen,
GarcíaMartínez Virginio,
Aránega Amelia E.,
Franco Diego
Publication year - 2015
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24309
Subject(s) - atrioventricular canal , microrna , biology , epithelial–mesenchymal transition , mesenchymal stem cell , microbiology and biotechnology , heart development , signal transduction , cancer research , transition (genetics) , medicine , gene , embryonic stem cell , genetics , heart disease
Background: Valve development is a multistep process involving the activation of the cardiac endothelium, epithelial‐mesenchymal transition (EMT) and the progressive alignment and differentiation of distinct mesenchymal cell types. Several pathways such as Notch/delta, Tgf‐beta and/or Vegf signaling have been implicated in crucial steps of valvulogenesis. We have previously demonstrated discrete changes in microRNAs expression during cardiogenesis, which are predicted to target Bmp‐ and Tgf‐beta signaling. We now analyzed the expression profile of 20 candidate microRNAs in atrial, ventricular, and atrioventricular canal regions at four different developmental stages. Results: qRT‐PCR analyses of microRNAs demonstrated a highly dynamic and distinct expression profiles within the atrial, ventricular, and atrioventricular canal regions of the developing chick heart. miR‐23b, miR‐199a, and miR‐15a displayed increased expression during early AVC development whereas others such as miR‐130a and miR‐200a display decreased expression levels. Functional analyses of miR‐23b, miR‐199a, and miR‐15a overexpression led to in vitro EMT blockage. Molecular analyses demonstrate that distinct EMT signaling pathways are impaired after microRNA expression, including a large subset of EMT‐related genes that are predicted to be targeted by these microRNAs. Conclusions: Our data demonstrate that miR‐23b and miR‐199a over‐expression can impair atrioventricular EMT. Developmental Dynamics 244:1259–1275, 2015 . © 2015 Wiley Periodicals, Inc.