Role of the miR-17∼92 cluster family in cerebellar and medulloblastoma development
| Autor: | Daisuke Kawauchi, Leila Ben Merzoug, Youngsoo Lee, Andrea Ventura, Olivier Ayrault, Martine F. Roussel, Peter J. McKinnon, Frederique Zindy |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Patched
Cerebellum Pathology medicine.medical_specialty QH301-705.5 Science Biology Development General Biochemistry Genetics and Molecular Biology Nestin medicine Progenitor cell Sonic hedgehog Granule neuron progenitors (GNPs) Biology (General) Receptor Medulloblastoma MicroRNA medicine.disease Molecular biology medicine.anatomical_structure PTCH1 embryonic structures miR-17∼92 and miR-106b∼25 clusters biology.protein General Agricultural and Biological Sciences Research Article |
| Zdroj: | Biology Open, Vol 3, Iss 7, Pp 597-605 (2014) Biology Open |
| ISSN: | 2046-6390 |
| Popis: | The miR-17∼92 cluster family is composed of three members encoding microRNAs that share seed sequences. To assess their role in cerebellar and medulloblastoma (MB) development, we deleted the miR-17∼92 cluster family in Nestin-positive neural progenitors and in mice heterozygous for the Sonic Hedgehog (SHH) receptor Patched 1 (Ptch1+/−). We show that mice in which we conditionally deleted the miR-17∼92 cluster (miR-17∼92floxed/floxed; Nestin-Cre+) alone or together with the complete loss of the miR-106b∼25 cluster (miR-106b∼25−/−) were born alive but with small brains and reduced cerebellar foliation. Remarkably, deletion of the miR-17∼92 cluster abolished the development of SHH-MB in Ptch1+/− mice. Using an orthotopic transplant approach, we showed that granule neuron precursors (GNPs) purified from the cerebella of postnatal day 7 (P7) Ptch1+/−; miR-106b∼25−/− mice and overexpressing Mycn induced MBs in the cortices of naïve recipient mice. In contrast, GNPs purified from the cerebella of P7 Ptch1+/−; miR-17∼92floxed/floxed; Nestin-Cre+ animals and overexpressing Mycn failed to induce tumors in recipient animals. Taken together, our findings demonstrate that the miR-17∼92 cluster is dispensable for cerebellar development, but required for SHH-MB development. |
| Databáze: | OpenAIRE |
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