Dicer-1 regulates proliferative potential of Drosophila larval neural stem cells through bantam miRNA based down-regulation of the G1/S inhibitor Dacapo.

The present work elucidates the role of miRNA in cell cycle regulation during brain development in Drosophila. Here we report that lineage specific depletion of dicer-1, a classically acknowledged miRNA biogenesis protein in neuroblasts leads to a reduction in their numbers and size in the third instar larval central brain. These brains also showed lower number of mitotically active cells and when homozygous mitotic clones were generated in an otherwise heterozygous dicer-1 mutant background via MARCM technique, they showed reduced number of progeny cells in individual clones, substantiating the adverse effect of the loss of dicer-1 on the proliferative potential of neuroblasts. bantam miRNA, which has been classically reported to be involved in tissue growth was found to express in neuroblasts and undergo reduced expression in Dicer-1 depleted background in the third instar larval brain. Reduction in the number and proliferative potential of neuroblasts in bantam mutant background implies a pivotal role played by bantam miRNA in maintenance of neuroblast number. Since, in both Dicer-1 and bantam depleted genetic backgrounds, Dacapo, an inhibitor of cyclin E-Cdk complex, was found to have elevated expression, we put forward a molecular mechanism involving bantam-Dacapo-Cyclin E/Cdk complex that regulates the G1-S phase transition of Drosophila neuroblasts.