Abstract
Development of the central nervous system (CNS) requires a precisely coordinated series of events. During embryonic development, different intra- and extracellular signals stimulate neural stem cells to become neural progenitors, which eventually irreversibly exit from the cell cycle to begin the first stage of neurogenesis. However, before this event occurs, the self-renewal and proliferative capacities of neural stem cells and neural progenitors must be tightly regulated. Accordingly, the participation of various evolutionary conserved microRNAs is key in distinct central nervous system (CNS) developmental processes of many organisms including human, mouse, chicken, frog, and zebrafish. microRNAs specifically recognize and regulate the expression of target mRNAs by sequence complementarity within the mRNAs 3′ untranslated region and importantly, a single microRNA can have several target mRNAs to regulate a process; likewise, a unique mRNA can be targeted by more than one microRNA. Thus, by regulating different target genes, microRNAs let-7, microRNA-124, and microRNA-9 have been shown to promote the differentiation of neural stem cells and neural progenitors into specific neural cell types while microRNA-134, microRNA-25 and microRNA-137 have been characterized as microRNAs that induce the proliferation of neural stem cells and neural progenitors. Here we review the mechanisms of action of these two sets of microRNAs and their functional implications during the transition from neural stem cells and neural progenitors to fully differentiated neurons. The genetic and epigenetic mechanisms that regulate the expression of these microRNAs as well as the role of the recently described natural RNA circles which act as natural microRNA sponges regulating post-transcriptional microRNA expression and function during the early stages of neurogenesis is also discussed.
Highlights
Embryonic stem cells (ESCs) are characterized by an unlimited self-renewal potential and are pluripotent as they are capable of originate cells of any tissue of the embryo (Gage, 2000; Liu et al, 2009; Xu et al, 2009)
There is evidence showing that a single TF or combination of certain TFs induces NSCs and/or NPs to differentiate into specific types of neurons within different regions of the mammalian brain as reported for Pax6 for differentiation of dopaminergic neurons in the olfactory bulb (Kohwi et al, 2005), neurogenin 3 (Ngn3) for POMC, NPY, TH, and SF1 neurons in the hypothalamus (Pelling et al, 2011), LIM homeobox 6 (Lhx6) for GABAergic interneurons and somatostatin (Sst) interneurons in the cortex (Neves et al, 2013) and LIM homeobox 7 (Lhx7) for cholinergic interneurons in the stratium (Lopes et al, 2012)
The concentration gradient of a single miRNA is capable of determining specific zones of neuronal differentiation as it is the case of miR-7 that maintains the proper localization of dopaminergic neuronal differentiation regions within the mouse olfactory bulb by having an opposite concentration/expression gradient to that of its target gene, Pax6 (De Chevigny et al, 2012)
Summary
Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, México. Different intra- and extracellular signals stimulate neural stem cells to become neural progenitors, which eventually irreversibly exit from the cell cycle to begin the first stage of neurogenesis. Before this event occurs, the self-renewal and proliferative capacities of neural stem cells and neural progenitors must be tightly regulated. We review the mechanisms of action of these two sets of microRNAs and their functional implications during the transition from neural stem cells and neural progenitors to fully differentiated neurons.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
