miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche

Cheng, Li-Chun; Pastrana, Érika; Tavazoie, Masoud; Doetsch, Fiona

doi:10.1038/nn.2294

Cited by 907 publications

(849 citation statements)

References 42 publications

Supporting

Mentioning

806

Contrasting

Unclassified

Order By: Relevance

“…Knocking out Sox9 in the developing mouse spinal cord results in perinatal lethality, decreased numbers of oligodendrocyte progenitors and astrocytes and an increased number of motor neurons (Stolt et al, 2003) and neuroblasts (Scott et al, 2010). MicroRNA studies also suggest that SOX9 is gliogenic, promoting neural stem cells to adopt an astrocyte or oligodendrocyte fate (Cheng et al, 2009). Following injury, neural stem cells proliferate and differentiate almost exclusively into astrocytes (Johansson et al, 1999;Meletis et al, 2008) that generate scar, but not into neurons (Johansson et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

McKillop

Dragan

Schedl

et al. 2012

Glia

View full text Add to dashboard Cite

Chondroitin sulfate proteoglycans (CSPGs) found in perineuronal nets and in the glial scar after spinal cord injury have been shown to inhibit axonal growth and plasticity. Since we have previously identified SOX9 as a transcription factor that upregulates the expression of a battery of genes associated with glial scar formation in primary astrocyte cultures, we predicted that conditional Sox9 ablation would result in reduced CSPG expression after spinal cord injury and that this would lead to increased neuroplasticity and improved locomotor recovery. Control and Sox9 conditional knock-out mice were subject to a 70 kdyne contusion spinal cord injury at thoracic level 9. One week after injury, Sox9 conditional knock-out mice expressed reduced levels of CSPG biosynthetic enzymes (Xt-1 and C4st), CSPG core proteins (brevican, neurocan, and aggrecan), collagens 2a1 and 4a1, and Gfap, a marker of astrocyte activation, in the injured spinal cord compared with controls. These changes in gene expression were accompanied by improved hind limb function and locomotor recovery as evaluated by the Basso Mouse Scale (BMS) and rodent activity boxes. Histological assessments confirmed reduced CSPG deposition and collagenous scarring at the lesion of Sox9 conditional knock-out mice, and demonstrated increased neurofilament-positive fibers in the lesion penumbra and increased serotonin immunoreactivity caudal to the site of injury. These results suggest that SOX9 inhibition is a potential strategy for the treatment of SCI.

show abstract

Section: Discussionmentioning

confidence: 99%

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

McKillop

Dragan

Schedl

et al. 2012

Glia

View full text Add to dashboard Cite

show abstract

“…For instance, 2′-O-methyl oligonucleotides have been shown to inhibit let-7b and miR-124, thereby inducing proliferation of neural stem cells [131]. Treatment with LNA antisense oligonucleotides decreased the levels of miR-21 in glioblastoma cell lines [132] and miR-219 in cortex [128,133].…”

Section: Microrna Therapymentioning

confidence: 99%

Epigenetics and ncRNAs in Brain Function and Disease: Mechanisms and Prospects for Therapy

2013

View full text Add to dashboard Cite

The most fundamental roles of non-coding RNAs (ncRNAs) and epigenetic mechanisms are the guidance of cellular differentiation in development and the regulation of gene expression in adult tissues. In brain, both ncRNAs and the various epigenetic gene regulatory mechanisms play a fundamental role in neurogenesis and normal neuronal function. Thus, epigenetic chromatin remodelling can render coding sites transcriptionally inactive by DNA methylation, histone modifications or antisense RNA interactions. On the other hand, microRNAs (miRNAs) are ncRNA molecules that can regulate the expression of hundreds of genes post-transcriptionally, typically recognising binding sites in the 3′ untranslated region (UTR) of mRNA transcripts. Furthermore, there are a myriad of interactions in the interface of miRNAs and epigenetics. For example, epigenetic mechanisms can silence miRNA coding sites, and miRNAs can be the effectors of transcriptional gene silencing, targeting complementary promoters or silencing the expression of epigenetic modifier genes like MECP2 and EZH2 leading to global changes in the epigenome. Alterations in this regulatory machinery play a key role in the pathology of complex disorders including cancer and neurological diseases. For example, miRNA genes are frequently inactivated by epimutations in gliomas. Here we describe the interactions between epigenetic and ncRNA regulatory systems and discuss therapeutic potential, with an emphasis on tumors, cognitive disorders and neurodegenerative diseases.

show abstract

“…SVZ type B cells continuously give rise to type C transit-amplifying cells themselves producing type A neuroblasts [30,31] that migrate tangentially along the RMS to the OB, where they differentiate into GABAergic neurons www.StemCells.com [32,33]. To determine how critical Cdk6 is for the proliferation of these neuronally committed precursor populations, we quantified the numbers of Dlx2 þ /DCX À /Ki-67 þ (type C) and Dlx2 þ /DCX þ /Ki-67 þ (type A) [34]. Both type C and type A proliferating precursors were reduced in the SVZ of Cdk6 À/À mice (Supporting Information Fig.…”

Section: Cdk6 Selectively Regulates the Proliferation Of Neuronally Cmentioning

confidence: 99%

Cdk6-Dependent Regulation of G1 Length Controls Adult Neurogenesis

et al. 2011

View full text Add to dashboard Cite

The presence of neurogenic precursors in the adult mammalian brain is now widely accepted, but the mechanisms coupling their proliferation with the onset of neuronal differentiation remain unknown. Here, we unravel the major contribution of the G 1 regulator cyclin-dependent kinase 6 (Cdk6) to adult neurogenesis. We found that Cdk6 was essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Specifically, Cdk6 deficiency prevents the expansion of neuronally committed precursors by lengthening G 1 phase duration, reducing concomitantly the production of newborn neurons. Altogether, our data support G 1 length as an essential regulator of the switch between proliferation and neuronal differentiation in the adult brain and Cdk6 as one intrinsic key molecular regulator of this process. STEM CELLS 2011;29:713-724 Disclosure of potential conflicts of interest is found at the end of this article.

show abstract

miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche

Cited by 907 publications

References 42 publications

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

Epigenetics and ncRNAs in Brain Function and Disease: Mechanisms and Prospects for Therapy

Cdk6-Dependent Regulation of G1 Length Controls Adult Neurogenesis

Contact Info

Product

Resources

About