The roles of Mcl-1 and Bcl-x in central nervous system development

Fogarty, Lauren Caroline (2015) The roles of Mcl-1 and Bcl-x in central nervous system development. Masters thesis, Memorial University of Newfoundland.

[English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (9MB)

Abstract

Changes in survival signaling through the stages of developmental neurogenesis are poorly understood. This thesis examined the role of anti-apoptotic Bcl-2 proteins, Mcl-1 and Bcl-x in promoting survival as cells progress through neurogenesis using Nestin-mediated conditional deletion of mcl-1, bcl-x or both in the mouse embryonic central nervous system. My results show Mcl-1 is required earlier in development in precursor populations, while Bcl-x is required for the post-mitotic cells. However, loss of a single bcl-x allele exasperated apoptotic death in the mcl-1 knockout revealing a novel role for Bcl-x in precursor cells. Furthermore, the double knockout exhibited a more severe phenotype with complete loss of the central nervous system. To determine ho Mcl-1 and Bcl-x promote cell survival, qPCR and in situ hybridization were used to examine the expression profiles of pro-apoptotic bcl-2 genes. This study demonstrates the distinct and overlapping requirements of Mcl-1 and bcl-x through murine neural development.

Actions (login required)

View Item