MicroRNAs Are Essential for the Developmental Switch from Neurogenesis to Gliogenesis in the Developing Spinal Cord

Zheng, Kang; Li, Hong; Zhu, Ying; Zhu, Qiang; Qiu, Mengsheng

doi:10.1523/jneurosci.1169-10.2010

Cited by 70 publications

(65 citation statements)

References 31 publications

(43 reference statements)

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“…Moreover, some of the same genes (e.g., Ascl1, Sox9) decline in the Dicer CKO progenitors in cerebral cortex and retina (38). Deletion of Dicer in spinal cord causes defects in the production of glia (40), similar to the loss of Müller glia in the retina. In embryonic stem cells and P19 cells, miR-9 and miR-125 increase during neural differentiation (41)(42)(43), and overexpression of miR-125 potentiates neural specification of human ESCs.…”

Section: Discussionmentioning

confidence: 99%

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Torre

Georgi²,

Reh

2013

Proc. Natl. Acad. Sci. U.S.A.

198

189

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Most regions of the vertebrate central nervous system develop by the sequential addition of different classes of neurons and glia. This phenomenon has been best characterized in laminated structures like the retina and the cerebral cortex, in which the progenitor cells in these structures are thought to change in their competence as development proceeds to generate different types of neurons in a stereotypic sequence that is conserved across vertebrates. We previously reported that conditional deletion of Dicer prevents the change in competence of progenitors to generate later-born cell types, suggesting that specific microRNAs (miRNAs) are required for this developmental transition. In this report, we now show that three miRNAs, let-7, miR-125, and miR-9, are key regulators of the early to late developmental transition in retinal progenitors: (i) members of these three miRNA families increase over the relevant developmental period in normal retinal progenitors; (ii) inhibiting the function of these miRNAs produces changes in retinal development similar to Dicer CKO; (iii) overexpression of members of these three miRNA families in Dicer-CKO retinas can rescue the phenotype, allowing their progression to late progenitors; (iv) overexpression of these miRNAs can accelerate normal retinal development; (v) microarray and computational analyses of Dicer-CKO retinal cells identified two potential targets of the late-progenitor miRNAs: Protogenin (Prtg) and Lin28b; and (vi) overexpression of either Lin28 or Prtg can maintain the early progenitor state. Together, these data demonstrate that a conserved miRNA pathway controls a key step in the progression of temporal identity in retinal progenitors.heterochronic | progenitor competence

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Section: Discussionmentioning

confidence: 99%

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Torre

Georgi²,

Reh

2013

Proc. Natl. Acad. Sci. U.S.A.

198

189

View full text Add to dashboard Cite

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“…miRNAs play essential roles in NSC differentiation and the cell fate switch between neurons and glia Hebert et al, 2010;Zheng et al, 2010). We have found that Dicer-deficient NSCs display abnormal differentiation, with shorter neurites in neurons and fewer processes in glial cells (Kawase-Koga et al, 2010) (Fig.…”

Section: Cell Fate Determination Controlled By Mirnasmentioning

confidence: 93%

“…Dicer ablation in the dopaminoceptive neurons in the basal ganglia using a dopamine receptor-1 ( DR-1)-Cre line leads to astrogliogenesis, but not neurodegeneration . Interestingly, in the mouse spinal cord, conditional deletion of Dicer using Olig1-Cre line disrupts production of both oligodendrocytes and astrocytes (Zheng et al, 2010). These observations suggest that global loss of miRNAs in specific precursor cells affects production of distinct cell types.…”

Section: Cell Fate Determination Controlled By Mirnasmentioning

confidence: 97%

Noncoding RNAs in Neural Stem Cell Development

Bian¹,

Sun²

2012

Neural Stem Cells and Therapy

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“…In the previous 2 years, studies have shown that the expression of many miRNAs is dynamically altered as OPCs differentiate into mature OLs [140,141]. Three studies used OL-specific promoters to knockout Dicer, a protein necessary for miRNA production, which essentially eliminates miRNAs from OL and OPCs [141][142][143]. The results revealed either a developmental disruption in gliogenesis [143] or that progenitor cells were formed but were unable to differentiate [141,142].…”

Section: Epigenetic and Post-translational Regulationmentioning

confidence: 99%

“…Three studies used OL-specific promoters to knockout Dicer, a protein necessary for miRNA production, which essentially eliminates miRNAs from OL and OPCs [141][142][143]. The results revealed either a developmental disruption in gliogenesis [143] or that progenitor cells were formed but were unable to differentiate [141,142]. Furthermore, the studies revealed that miRNAs decrease expression of proteins needed to maintain cells in a proliferative state.…”

Section: Epigenetic and Post-translational Regulationmentioning

confidence: 99%

Oligodendrocyte Fate after Spinal Cord Injury

2011

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Summary: Oligodendrocytes (OLs) are particularly susceptible to the toxicity of the acute lesion environment after spinal cord injury (SCI). They undergo both necrosis and apoptosis acutely, with apoptosis continuing at chronic time points. Loss of OLs causes demyelination and impairs axon function and survival. In parallel, a rapid and protracted OL progenitor cell proliferative response occurs, especially at the lesion borders. Proliferating and migrating OL progenitor cells differentiate into myelinating OLs, which remyelinate demyelinated axons starting at 2 weeks postinjury. The progression of OL lineage cells into mature OLs in the adult after injury recapitulates development to some degree, owing to the plethora of factors within the injury milieu. Although robust, this endogenous oligogenic response is insufficient against OL loss and demyelination. First, in this review we analyze the major spatial-temporal mechanisms of OL loss, replacement, and myelination, with the purpose of highlighting potential areas of intervention after SCI. We then discuss studies on OL protection and replacement. Growth factors have been used both to boost the endogenous progenitor response, and in conjunction with progenitor transplantation to facilitate survival and OL fate. Considerable progress has been made with embryonic stem cellderived cells and adult neural progenitor cells. For therapies targeting oligogenesis to be successful, endogenous responses and the effects of the acute and chronic lesion environment on OL lineage cells must be understood in detail, and in relation, the optimal therapeutic window for such strategies must also be determined.

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MicroRNAs Are Essential for the Developmental Switch from Neurogenesis to Gliogenesis in the Developing Spinal Cord

Cited by 70 publications

References 31 publications

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Noncoding RNAs in Neural Stem Cell Development

Oligodendrocyte Fate after Spinal Cord Injury

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