“The scientist, by the very nature of his commitment, creates more and more questions, never fewer. Indeed the measure of our intellectual maturity, one philosopher suggests, is our capacity to feel less and less satisfied with our answers to better problems.”
~G.W. Allport, Becoming, 1955
It will be interesting to look back at this thesis in a few decades and reflect on how the questions and interpretation of data in the field of developmental biology have changed. Indeed, a biologist currently in their twilight years might reflect on their youth, before the discovery of hereditary material, and compare that bookend with the range of genome sequences and related knowledge currently available. How long will it take before this thesis reads like a debate about whether the male or female contributed the ‘homunculus,’ a miniature preformed human to the embryo that grows into an adult?
In this thesis I asked three related questions: whether the role of Oct4 during embryogenesis provides insight into its contribution to pluripotency; how surfaceome changes contribute to functional maturation of neural stem cells and to what extent the murine genome is imprinted. Our data indicate that Oct4 is required for posterior expansion. We propose that the function of the protein is conserved, but that its expression has been coopted to yield different cell types based on its combination with different factors. We show that fundamental aspects of cell biology are altered during the maturation from pluripotent populations to neural stem cells, and identify mediators of proliferation, survival and adhesion that distinguish neural stem cell regulation from their precursors. Finally, we validated discovery of a dozen novel imprinted transcripts using a genomic approach. These discoveries will contribute to a holistic view of the causes and consequences of imprinting, but do not support a paradigm shift in the scale and consequences of imprinting.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/65504 |
| Date | 20 June 2014 |
| Creators | DeVeale, Brian |
| Contributors | van der Kooy, Derek |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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