Dicer1 and MiR‐9 are required for proper Notch1 signaling and the Bergmann glial phenotype in the developing mouse cerebellum

Kuang, Yi; Liu, Qian; Shu, Xiaoqiong; Zhang, Chi; Huang, Ning; Li, Jun; Jiang, Mei; Li, Hedong

doi:10.1002/glia.22392

Cited by 37 publications

(52 citation statements)

References 57 publications

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“…This miRNA has previously been identified as expressed during the gastrula and larval stages of C. robusta (Hendrix et al, 2010). In other species miR-9 has been shown to regulate differentiation via targeting of the Notch signaling pathway (Jing et al, 2011;Kuang et al, 2012). The proliferative state of neural progenitors is governed by oscillations in the protein level of Hes1; high levels of miR-9 were shown to dampen oscillations of Hes1 leading to increased proliferation and differentiation (Bonev et al, 2012;Tan et al, 2012).…”

Section: Discussion Molecular Signatures Indicate Conserved Features mentioning

confidence: 99%

A microRNA-mRNA expression network during oral siphon regeneration in Ciona

et al. 2017

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Here we present a parallel study of mRNA and microRNA expression during oral siphon (OS) regeneration in Ciona robusta, and the derived network of their interactions. In the process of identifying 248 mRNAs and 15 microRNAs as differentially expressed, we also identified 57 novel microRNAs, several of which are among the most highly differentially expressed. Analysis of functional categories identified enriched transcripts related to stress responses and apoptosis at the wound healing stage, signaling pathways including Wnt and TGFβ during early regrowth, and negative regulation of extracellular proteases in late stage regeneration. Consistent with the expression results, we found that inhibition of TGFβ signaling blocked OS regeneration. A correlation network was subsequently inferred for all predicted microRNA-mRNA target pairs expressed during regeneration. Network-based clustering associated transcripts into 22 non-overlapping groups, the functional analysis of which showed enrichment of stress response, signaling pathway and extracellular protease categories that could be related to specific microRNAs. Predicted targets of the miR-9 cluster suggest a role in regulating differentiation and the proliferative state of neural progenitors through regulation of the cytoskeleton and cell cycle.

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Section: Discussion Molecular Signatures Indicate Conserved Features mentioning

confidence: 99%

A microRNA-mRNA expression network during oral siphon regeneration in Ciona

et al. 2017

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“…The generation of hGFAP‐Cre;Dicer1 f/f and hGFAP‐Cre;Dicer1 f/+ mouse lines with a LacZ reporter and their genotyping were described previously (Kuang et al, ). All animal use and studies were approved by the Institutional Animal Care and Use Committee of West China 2nd Hospital, Developmental & Stem Cell Institute, Sichuan University, Chengdu, People's Republic of China.…”

Section: Methodsmentioning

confidence: 99%

“…RNA extraction and qRT‐PCR were performed as described (Kuang et al, ). Primer sequences of target genes are shown in Table .…”

Section: Methodsmentioning

confidence: 99%

Functional requirement of dicer1 and miR‐17‐5p in reactive astrocyte proliferation after spinal cord injury in the mouse

Hong

Jiang

2014

Glia

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Reactive astrogliosis after spinal cord injury (SCI) contributes to glial scar formation that impedes axonal regeneration. The mechanisms underlying reactive astrocyte proliferation upon injury remain partially understood. MicroRNAs (miRNAs) function as a major class of post-transcriptional gene expression regulators that participate in many biological processes. However, miRNA function during reactive astrogliosis, particularly in injury-induced astrocyte proliferation, has not been carefully examined. In this study, we conditionally deleted Dicer1 gene encoding an enzyme that is required for mature miRNA generation, and examined the proliferative behavior of Dicer1-null reactive astrocytes in the transected mouse spinal cord. We found that injury-induced proliferation is blocked in Dicer1-null astrocytes. Previous reports indicate that miR-17-5p family members are upregulated during SCI. We therefore tested functional contribution of miR-17-5p to the proliferation of reactive astrocytes in vitro. Our results showed that a synthetic miR-17-5p mimic is able to rescue the proliferation defect of Dicer1-null astrocytes, while an antisense inhibitor of miR-17-5p blocked lipopolysaccharide-induced astrocytic proliferation. Similar results are also observed in leukemia inhibitory factor (LIF)-treated astroglial cultures suggesting that miR-17-5p particularly modulates reactive astrocyte proliferation initiated by LIF presumably via the JAK/STAT3 pathway. Furthermore, overexpression of miR-17-5p leads to decrease of several cell cycle regulators in cultured astroglia and astrocytoma cell line C6. Our conclusion is that miRNAs are indispensable to the injury-induced reactive astrocyte proliferation, and that miR-17-5p may be a major player regulating this pathological process by affecting cell cycle machinery.

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“…We bred Aspm f/f mice into the rapidly tumorigenic medulloblastoma model, hGFAP-Cre;SmoM2 (G-Smo). G-Smo mice express a constitutively active allele of the Shh receptor component Smo (Mao et al, 2006) in stem cells that give rise to the neurons and glia of the cerebrum and cerebellum excluding the Purkinje cells (Zhuo et al, 2001;Kuang et al, 2012), and develop medulloblastoma with 100% incidence, dying of tumor progression by P20 (Schüller et al, 2008). We investigated the effect of Aspm To compare tumor size, we measured tumor cross-sectional area, normalized to the cross-sectional area of non-tumor cerebellum.…”

Section: Aspm Deficiency Slows the Growth Of Medulloblastomamentioning

confidence: 99%

Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth

et al. 2015

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Alterations in genes that regulate brain size may contribute to both microcephaly and brain tumor formation. Here, we report that Aspm, a gene that is mutated in familial microcephaly, regulates postnatal neurogenesis in the cerebellum and supports the growth of medulloblastoma, the most common malignant pediatric brain tumor. Cerebellar granule neuron progenitors (CGNPs) express Aspm when maintained in a proliferative state by sonic hedgehog (Shh) signaling, and Aspm is expressed in Shh-driven medulloblastoma in mice. Genetic deletion of Aspm reduces cerebellar growth, while paradoxically increasing the mitotic rate of CGNPs. Aspm-deficient CGNPs show impaired mitotic progression, altered patterns of division orientation and differentiation, and increased DNA damage, which causes progenitor attrition through apoptosis. Deletion of Aspm in mice with Smo-induced medulloblastoma reduces tumor growth and increases DNA damage. Co-deletion of Aspm and either of the apoptosis regulators Bax or Trp53 (also known as p53) rescues the survival of neural progenitors and reduces the growth restriction imposed by Aspm deletion. Our data show that Aspm functions to regulate mitosis and to mitigate DNA damage during CGNP cell division, causes microcephaly through progenitor apoptosis when mutated, and sustains tumor growth in medulloblastoma.

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Dicer1 and MiR‐9 are required for proper Notch1 signaling and the Bergmann glial phenotype in the developing mouse cerebellum

Cited by 37 publications

References 57 publications

A microRNA-mRNA expression network during oral siphon regeneration in Ciona

A microRNA-mRNA expression network during oral siphon regeneration in Ciona

Functional requirement of dicer1 and miR‐17‐5p in reactive astrocyte proliferation after spinal cord injury in the mouse

Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth

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