Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.652868
Title: The role of Apc in cortical development
Author: Ivaniutsin, U.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Abstract:
This thesis is devoted to examining the role of Apc protein in the development of the mouse telencephalon. As Apc-/- embryos die at gastrulation, a conditional knock-out approach was used to examine Apc’s role in cortical development. Mutant mice with conditional (flowed) alleles of Apc were crossed to a strain in which Cre expression is driven by the Emx1 promoter (Emx1Cre), allowing specific deletion of Apc in the dorsal telencephalon. The current work presents a detailed description and possible explanations of Apc’s functions in the developing cerebral cortex. Conditional knock-out of Apc in the cortex led to severe developmental defects in this region, showing that Apc is required for normal development of the cerebral cortex. The deletion of Apc leads to over-activation of the canonical Wnt pathway and disregulation of PCP Wnt pathway. I examined the expression of regional markers in the residual dorsal telencephalon in conditional Apc mutant embryos. Expression of Foxg1 is lost, showing that the mutant dorsal telencephalon loses telencephalic identify from E12.5. My data show that Apc is important for proper patterning of the cortex probably mostly by antagonizing the canonical Wnt pathway. Measurement of cell-cycle times revealed that in the absence of Apc, S-phase and cell cycle length remains similar to controls. Deletion of Apc in the dorsal telencephalon leads to defects in maintenance of the size of the progenitor pool and regulation of apoptosis. The conditional Apc deletion has a pleiotropic effect on cortical development. Developmental defects found include disregulation of Wnt signalling, loss of cell polarity, adhesion defects, cell identify defects, and disregulation of apoptosis. Assignment of these defects to particular functions of Apc is not completely clear yet.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.652868  DOI: Not available
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