Date of Award

2012

Degree Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

First Advisor

Lisa A Porter

Second Advisor

Elizabeth Fidalgo da Silva

Keywords

Cell Fate, Neural Development, Tuberin, Tuberous Sclerosis

Rights

CC-BY-NC-ND 4.0

Abstract

Inhibition or misregulation of the tumour suppressor protein Tuberin is known to cause the benign tumour disorder Tuberous Sclerosis, involving developmental defects in many organ systems including the central nervous system. Data supports that appropriate control of Tuberin levels may play an essential role in the regulation of neural fate decisions. Hence, this work investigates the regulation of Tuberin through neural development both in vitro, using SH-SY5Y and RN33B neuronal precursor cells, and in vivo using murine neural tissues. We demonstrate that Tuberin expression and activity are significantly down-regulated during neuronal differentiation in vitro, and during aging in vivo, in a cell and tissue specific manner. We have developed tools needed to address the essentiality of Tuberin in neural differentiation in vitro and to begin to dissect the molecular pathways affected. Understanding how Tuberin is regulated through neural development is necessary in understanding the developmental defects and pathologies associated with Tuberous Sclerosis.

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