MiRNA-128 regulates the proliferation and neurogenesis of neural precursors by targeting PCM1 in the developing cortex

Abstract

During the development, tight regulation of the expansion of neural progenitor cells (NPCs) and their differentiation into neurons is crucial for normal cortical formation and function. In this study, we demonstrate that microRNA (miR)-128 regulates the proliferation and differentiation of NPCs by repressing pericentriolar material 1 (PCM1). Specifically, overexpression of miR-128 reduced NPC proliferation but promoted NPC differentiation into neurons both in vivo and in vitro. In contrast, the reduction of endogenous miR-128 elicited the opposite effects. Overexpression of miR-128 suppressed the translation of PCM1, and knockdown of endogenous PCM1 phenocopied the observed effects of miR-128 overexpression. Furthermore, concomitant overexpression of PCM1 and miR-128 in NPCs rescued the phenotype associated with miR-128 overexpression, enhancing neurogenesis but inhibiting proliferation, both in vitro and in utero. Taken together, these results demonstrate a novel mechanism by which miR-128 regulates the proliferation and differentiation of NPCs in the developing neocortex.DOI: http://dx.doi.org/10.7554/eLife.11324.001

Regulation of centriolar satellite integrity and its physiology

“…One recent report [140] shows that a microRNA, called miR-128, negatively regulates the cellular levels of PCM1. Overexpression of miR-128 resulted in downregulation of PCM1, leading to repressing proliferation of neural progenitor cells yet simultaneously promoting their differentiation into neurons.…”

“…Overexpression of miR-128 resulted in downregulation of PCM1, leading to repressing proliferation of neural progenitor cells yet simultaneously promoting their differentiation into neurons. Conversely, the reduction of miR-128 elicited the opposite effects; promotion of proliferation and suppression of differentiation of neural progenitor cells [140]. Whether this inhibitory role of PCM1 in neurogenesis is exerted through centriolar satellite integrity is yet to be rigorously examined, but this would be a novel, intriguing aspect of the physiology of centriolar satellites.…”

Human-specific genomic signatures of neocortical expansion

“…MicroRNAs (miRNAs) have emerged as important regulators of NPC proliferation and neocortex size [66][67][68][69][70][71][72].…”

MicroRNA-128 Protects Dopamine Neurons from Apoptosis and Upregulates the Expression of Excitatory Amino Acid Transporter 4 in Parkinson’s Disease by Binding to AXIN1

“…Furthermore, miR-128 has been shown to be downregulated in glioma, in which overexpressed miR-128 reduces neuroblastoma cell motility and invasiveness by inhibiting Reelin and DCX and inhibits cell proliferation by targeting E2F3a and Bmi-1 (apoptosisrelated genes) [28]. Overexpressed miR-128 suppresses the proliferation of neural progenitor cells while facilitating the differentiation of neural progenitor cells to neurons and regulates the neurogenesis of neural precursors by targeting PCM1 in the developing cortex [29]. In addition, Karam et al reported that miR-128 is induced in the differentiation of neuronal cells and during brain development, which contributes to the inhibition of nonsensemediated decay, and the regulation of mRNAs that encode proteins are strongly related to neuron differentiation and function [30].…”