MicroRNAs in Palatogenesis and Cleft Palate.

Christian Schoen,Johannes W Von Den Hoff,Michelle Thonissen,Carine E L Carels,Geert Poelmans,Armaz Aschrafi

doi:10.3389/fphys.2017.00165

Abstract

Palatogenesis requires a precise spatiotemporal regulation of gene expression, which is controlled by an intricate network of transcription factors and their corresponding DNA motifs. Even minor perturbations of this network may cause cleft palate, the most common congenital craniofacial defect in humans. MicroRNAs (miRNAs), a class of small regulatory non-coding RNAs, have elicited strong interest as key regulators of embryological development, and as etiological factors in disease. MiRNAs function as post-transcriptional repressors of gene expression and are therefore able to fine-tune gene regulatory networks. Several miRNAs are already identified to be involved in congenital diseases. Recent evidence from research in zebrafish and mice indicates that miRNAs are key factors in both normal palatogenesis and cleft palate formation. Here, we provide an overview of recently identified molecular mechanisms underlying palatogenesis involving specific miRNAs, and discuss how dysregulation of these miRNAs may result in cleft palate.

Highlights

Cleft palate represents the most common craniofacial birth defect, occurring on its own, in combination with a cleft lip or as part of a genetic syndrome (Mossey and Modell, 2012)
We provide an overview of the emerging concepts on the roles of miRNAs during palatogenesis and cleft palate
MiRNAs are small non-coding RNAs that function as post-transcriptional repressors. They are essential for embryonic development, and depletion of miRNAs in the mesenchyme and oral ectoderm of mouse embryos leads to cleft palate

Summary

Introduction

Cleft palate represents the most common craniofacial birth defect, occurring on its own, in combination with a cleft lip or as part of a genetic syndrome (Mossey and Modell, 2012). It is interesting to note that DGCR8 is strongly expressed in the developing PS of mice but further studies are needed to elucidate the role in normal palatogenesis and cleft palate formation (Shiohama et al, 2003). By using the promoter of Pitx2, a gene that is expressed in the oral ectoderm as early as E10.5, for the conditional deletion of Dicer, a cleft palate with incomplete penetrance develops, in addition to several dental defects (Cao et al, 2010).

Results

Conclusion