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The Identification and Characterization of Evolutionarily Conserved Transcription Factors Required for Brain Regeneration in Flatworm

Posted on:2019-04-02Degree:Ph.DType:Thesis
University:University of Toronto (Canada)Candidate:Brown, DavidFull Text:PDF
GTID:2444390002499723Subject:Developmental Biology
Abstract/Summary:
Powerful genetic tools in classical laboratory models have been fundamental to our understanding of how stem cells give rise to complex neural tissues during embryonic development. In contrast, adult neurogenesis in our model systems, if present, is typically constrained to one or a few zones of the adult brain to produce a limited subset of neurons leading to the dogma that the brain is primarily fixed post-development. The freshwater planarian (flatworm) is an invertebrate model system that challenges this dogma through its continuous neuronal cell turnover and the ability to rapidly regenerate a brain de novo after injury. My aims in this thesis were to identify and characterize regulators of flatworm regenerative adult neurogenesis to gain a deeper understanding of the fundamentals of unlimited adult regenerative neurogenesis. I found that members of the basic helix-loop-helix gene family are required to regenerate a brain. Additionally, I identified a planarian TCF/LEF transcription factor Smed-tcf1 as required for the proper regeneration of several dorsal-lateral neural populations including GABAergic neurons.
Keywords/Search Tags:Required, Brain
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