MiR-9 and the Midbrain-Hindbrain Boundary: A Showcase for the Limited Functional Conservation and Regulatory Complexity of MicroRNAs

A Alwin Prem Anand,Gonzalo Alvarez-Bolado,Andrea Wizenmann

doi:10.3389/fcell.2020.586158

A Alwin Prem Anand, Gonzalo Alvarez-Bolado + Show 1 more

Open Access

https://doi.org/10.3389/fcell.2020.586158

Copy DOI

Abstract

MicroRNAs regulate gene expression at post-transcriptional levels. Some of them appear to regulate brain development and are involved in neurodevelopmental disorders. This has led to the suggestion that the role of microRNAs in neuronal development and function may be more central than previously appreciated. Here, we review the data about miR-9 function to depict the subtlety, complexity, flexibility and limited functional conservation of this essential developmental regulatory system. On this basis we propose that species-specific actions of miR-9 could underlie to a large degree species differences in brain size, shape and function.

Highlights

MicroRNAs are short non-coding RNA oligonucleotides (18–25 bases), which regulate gene expression at post-transcriptional levels by binding specific mRNAs and in this way marking them for enzymatic destruction
The results show that miR-9 is essential for proper neural differentiation but that its effect is not uniform in all vertebrate models and cannot be generalized
In Xenopus, the function of miR-9 promoting neurogenesis and antagonizing proliferation is mediated by decreasing the availability of Hairy1 but while in the forebrain the final effect of this decrease is mediated by Fgf8, in the hindbrain it is mediated by Wnt (Bonev et al, 2011)

Summary

Introduction

MicroRNAs (miRNAs, miRs) are short non-coding RNA oligonucleotides (18–25 bases), which regulate gene expression at post-transcriptional levels by binding specific mRNAs and in this way marking them for enzymatic destruction (reviewed in Pasquinelli, 2012). MiR-9 targeting of her/hairy/hes is necessary to properly balance progenitor proliferation genes in zebrafish, Xenopus and mouse (Leucht et al, 2008; Bonev et al, 2011, 2012; Coolen et al, 2012). Interesting is the fact that miR-9 can regulate different target pathways in forebrain and hindbrain, to obtain region-specific results (Bonev et al, 2011).

Results

Conclusion