The anti-apoptotic role of Mcl-1 during early nervous system development

Flemmer, Robert T. (2019) The anti-apoptotic role of Mcl-1 during early nervous system development. Masters thesis, Memorial University of Newfoundland.

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Developmental neurogenesis, the formation of neurons in utero, is tightly regulated by apoptosis, a form of programmed cell death. The pro-survival protein Mcl-1 has been shown to be important for the survival of the developing nervous system through its ability to inhibit apoptosis. This dependency is poorly understood. Moreover, how Mcl-1 inhibits apoptosis in the developing nervous system is unknown. Here, conditional ablation of mcl-1 in the murine developing nervous system (Mcl-1 CKO) resulted in widespread death throughout the developing nervous system. Mcl-1 CKOs showed a progression of apoptosis that mirrors the progression of differentiation in the brainstem and spinal cord. Apoptosis was rescued by co-deleting pro-apoptotic Bax in Mcl-1 CKO mice, demonstrating that Mcl-1 promotes cell survival by blocking the activation of Bax. This work is the first to demonstrate widespread dependency on Mcl-1 during early nervous system development.

Item Type: Thesis (Masters)
Item ID: 13782
Additional Information: Includes bibliographical references (pages 91-112).
Keywords: Neuroscience, Neurogenesis, Development, Cell Death, Apoptosis, Bcl-2 family, Mcl-1, Bax, Embryonic lethal
Department(s): Medicine, Faculty of > Biomedical Sciences
Date: May 2019
Date Type: Submission
Digital Object Identifier (DOI):
Medical Subject Heading: Neurosciences; Neurogenesis; Cell Death; Embryonic Structures

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