Dicer endoribonuclease catalyzes the maturation of microRNAs (miRNAs) from
double stranded precursors. Studies conditionally inactivating Dicer in the mouse
embryonic forebrain continue to shed light on the spectrum of biological processes
subject to miRNA regulation.
This study looked at defects of brain development following a widespread ablation
of Dicer in the early forebrain. The neuroepithelial stem cells failed to specify the
radial glia appropriately around the time when the first postmitotic neurons begin to
be generated in the neuroepithelium.
Ablation of Dicer in only a subset of radial glia was not accompanied by the early
apoptosis observed in all other models of Dicer ablation in the cortex. This allowed
the study of the role of miRNAs in regulating cell numbers in the cortex. The study
revealed that generation of cortical cells is increased during postnatal development.
Finally, the study identified a miRNA which is able to negatively regulate the
development of neuronal precursor cells of the developing cortex by targeting Tbox
transcription factor 2.
Together the results presented in this Thesis contribute to the understanding of the
roles of endogenous RNA interference in the development of the brain