Genetic regulation of the generation of neuronal diversity in the developing mammalian basal forebrain
Cocas, Laura A.
Thesis (Ph.D.)--Georgetown University, 2010.; Includes bibliographical references.; Text (Electronic thesis) in PDF format. The forebrain is the structure that is most implicated in complex mammalian behaviors: consciousness, reason, language, memory, and emotionality are all the result of cellular and molecular processes in this region of the brain. The telencephalon is the embryonic precursor to the forebrain; through several developmental mechanisms, including the patterning of progenitor domains, and the proliferation, migration, and specification of neuronal subtypes, the telencephalon gives rise to a complex and highly ordered functional network made up of a diversity of neuronal subtypes that process and integrate information and control behavior. The molecular mechanisms by which this brain region is formed during embryonic development are still being explored. We sought to examine the mechanisms used in the development of forebrain neuronal diversity by examining several important developmental questions using a combination of genetic fate-mapping, mutagenesis, cell birth-dating, migration assays, immunohistochemistry, and electrophysiology. We examined the genetic regulation of border formation in the telencephalon, and the impact that the correct patterning of this structure has on the fate of cells in the forebrain. We found that genetic regulation of border formation is critical for dorsal ventral patterning and is necessary for the correct generation of excitatory and inhibitory neuronal subpopulations in the amygdala and olfactory bulb. We also examined the importance of embryonic development on the fate of cells in the postnatal forebrain, and found that the generation of neuronal diversity in the amygdala, striatum, and olfactory bulb is regulated by interactions between several biological processes, including the origin and timing of progenitor cell birth, combinatorial codes of transcription factor expression, and diverse migratory pathways.
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