Role of the miR-17 92 cluster family in cerebellar and medulloblastoma development

  • Zindy F
  • Kawauchi D
  • Lee Y
  • et al.
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Abstract

© 2014, Company of Biologists Ltd. All rights reserved. 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-17-92 floxed/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-17-92 floxed/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.

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Zindy, F., Kawauchi, D., Lee, Y., Ayrault, O., Ben Merzoug, L., McKinnon, P. J., … Roussel, M. F. (2014). Role of the miR-17 92 cluster family in cerebellar and medulloblastoma development. Biology Open, 3(7), 597–605. https://doi.org/10.1242/bio.20146734

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