MicroRNAs in adult and embryonic neurogenesis - PubMed (original) (raw)

Review

MicroRNAs in adult and embryonic neurogenesis

Changmei Liu et al. Neuromolecular Med. 2009.

Abstract

Neurogenesis is defined as a process that includes the proliferation of neural stem/progenitor cells (NPCs) and the differentiation of these cells into new neurons that integrate into the existing neuronal circuitry. MicroRNAs (miRNAs) are a recently discovered class of small non-protein coding RNA molecules implicated in a wide range of diverse gene regulatory mechanisms. More and more data demonstrate that numerous miRNAs are expressed in a spatially and temporally controlled manners in the nervous system, which suggests that miRNAs have important roles in the gene regulatory networks involved in both brain development and adult neural plasticity. This review summarizes the roles of miRNAs-mediated gene regulation in the nervous system with focus on neurogenesis in both embryonic and adult brains.

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Figures

Fig. 1

Currently known functions of let-7 miRNA in stem cell self-renewal

Fig. 2

Schematic summary showing how miR-124 may modulate multiple pathways involved in neuronal neurogenesis through translational regulation of its currently known mRNA targets. Polypyrimidine tract binding protein 1 (PTBP1) is a global repressor of alternative pre-mRNA splicing in non-neuronal cells. One target of PTBP1 is a critical exon in the pre-mRNA of PTBP2. When PTBP1 level is high, it inhibits neuronal PTBP2 protein level by alternative splicing. miR-124 down regulates PTBP1 therefore upregulates the level of PTBP2 in cells undergoing neuronal differentiation. Small C-terminal domain phosphatase 1 (SCP1) is an anti-neural factor expressed in non-neural tissues. Neuronal restricted silencing factor/ RE-1 Silencing Transcription factor (REST) recruits SCP1 to RE1-containing neural genes (including miR-124) and repress their expression. miR-124 down regulates SCP1, which also ensure its own expression. Sox9 has been shown to promote expression of gilal genes and to maintain stem cell niche. Down regulation of Sox9 has been clearly demonstrated to promote neuronal differentiation (please see text for details and references)

Fig. 3

Studying functions of mRNAs in neurogenesis using recombinant viruses. Both lentivirus and retrovirus can be engineered to express both miRNAs and GFP (top panel). Production of these viruses can be achieved by transfecting into 293T cells. Lentivirus can infect cultured primary NSCs at high efficiency and infected cells expressing miRNA (also GFP+) can be analyzed for their proliferation and differentiation potential (left panel). Retrovirus infect only diving cells therefore can be used to label dividing neuroprogenitors in adult brains. The labeled cells can then be tracked for their differentiation (1 week post injection) and neuronal maturation (4 weeks post injection) capabilities (right panel). BrdU, bromodeoxyuridine used to label dividing cells. Cell lineage markers used for flurescent imaging: TuJI, a marker for immature neurons. GFAP, a marker for astrocytes; NeuN, a marker for mature neurons; DCX, a marker for immature neurons; DAPI, a nuclear dye

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MicroRNAs in adult and embryonic neurogenesis - PubMed (original) (raw)