Price, David

Mason, John

Pratt, Thomas

Nowakowski, Tomasz Jan

2014-10-03T12:56:13Z

2014-10-03T12:56:13Z

2012-06-22

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.

http://hdl.handle.net/1842/9471

en

The University of Edinburgh

Nowakowski, T. J., Mysiak, K. S., Pratt, T. and Price, D. J. (2011). Functional dicer is necessary for appropriate specification of radial glia during early development of mouse telencephalon. PLoS One 6, e23013.

microRNA

dicer endoribonuclease

miRNA regulation

brain development

Roles of the microRNA pathway in cortical development

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy