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.

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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.

Item Type: Thesis (Masters)
URI: http://research.library.mun.ca/id/eprint/11567
Item ID: 11567
Additional Information: Includes bibliographical references (pages 113-125).
Keywords: Mcl-1, Bcl-x, apoptosis, central nervous system, Bcl-2 family
Department(s): Medicine, Faculty of > Biomedical Sciences
Date: October 2015
Date Type: Submission
Library of Congress Subject Heading: Developmental neurobiology; Cells--Growth--Regulation; Apoptosis; Central nervous system--Growth--Regulation

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