Mammalian brain development
Subtitle: the role of distinct neural stem and progenitor cells from embryonic neural induction to adult neurogenesis.
Published: 2004
Language: eng
Number of pages: 267
Description: One of the most intriguing mysteries of mammalian development is how the pluripotent cells of the inner cell mass become restricted in potential and generate the many differentiated cell types of complex tissues, such as the brain. In this thesis, I explore the early cell types involved at the outset of this process, and present evidence suggesting that primitive and definitive neural stem cells can be successively derived from pluripotent ES cells, and further that these neural stem cells differ in terms of their gene expression patterns and ability to generate non-neural tissues. I posit that these characteristics vary as a function of exposure to LIF and level of Oct4 expression. In harmony with the early neural lineage model that has evolved from in vitro studies, I also report the clonal isolation of primitive neural stem cells directly from the early murine epiblast. As development proceeds, neural stem cells become restricted to specific brain regions. In the early postnatal period, I demonstrate that neural precursor cells that are transiently neuronogenic can be isolated from many brain regions, including those in which neurogenesis has been completed (such as the striatum and cortex) as well as from one region that is never a site of neurogenesis (optic nerve). However, these cells do not exhibit self-renewal in vivo nor maintenance of multipotentiality in vitro or in vivo, and thus are more aptly termed restricted neural progenitors. I argue that fundamental biological differences exist between neural stem and progenitor cells, and that both cell types persist into adulthood and are responsible for the continued generation of new neurons in the adult brain. Specifically, I provide evidence that neural stem cells and restricted neuronal progenitors underlie olfactory bulb and dentate gyrus neurogenesis, respectively. Finally, I suggest that the definitions of stem and progenitor cell are applicable to other tissue systems, and describe a novel adult pancreatic progenitor cell that is capable of generating multiple differentiated cell types of both pancreatic and neural lineages.
Notes: Adviser:  Derek van der Kooy.

Thesis (Ph.D.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Dissertation Abstracts International, Volume: 65-05, Section: B, page: 2282.