Determinants of cerebral cortical progenitor growth and differentiation : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
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[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2005]
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| Subjects: |
| Abstract: | ABSTRACT: A fundamental question in developmental biology relates to how cellular diversity is achieved from small populations of stem cells during histogenesis. In the developing central nervous system, millions of neurons and glia are elaborated from a relatively small population of neuronal stem cells that reside in the neuroepithelium of the cranial neural tube (Bayer and Altman, 1991). From their origins in the neuroepithelium, newly generated neurons exit the ventricular zone and migrate toward the pial surface to form the cortical plate, the structural precursor of the cerebral cortex. Iterations of the process are germane to the generation of neuronal diversity and to the normal development of the cerebral cortex. Research has revealed many of the mechanisms that permit neuroepithelial stem cells to divide and retain their stem-like qualities, or differentiate into neurons. Yet elusive, however, is a depiction of how these genetic mechanisms become initially activated to induce polarity in what is otherwise a homogeneous neuroepithelial sheet consisting of undifferentiated progenitor cells. It has been suggested that the developing cortical neuroepithelium contains a "protomap" (Donoghue and Rakic, 1999) of the adult cortex, and that the diversification of the stem cell pool within the neuroepithelium itself is the principle determinant of the final pattern of the adult cerebral cortex. The studies presented here aim to understand the mechanisms that initiate cell fate determination during cerebral cortical development. In the hematopoetic system, stem cell antigens identify cells in various stages of developmental transition, and thus, antigen expression reflects the status of development along a competency continuum. These antigens are also expressed in embryonic brain regions involved in neurogenesis, suggesting that a range of developmental competency also exists during neuroepithelial expansion. The work herein attempts to deconstruct the cortical neuroepithelial protomap and define the intrinsic cellular heterogeneity of neuroepithelial cells. The developmental consequences of perturbations to the balance between different cortical stem cell populations have not been addressed in experimental systems of drug abuse, namely alcohol-induced brain damage. Studies which examine the extent to which alcohol, a common cause of prenatal brain damage, disrupts cortical stem cell heterogeneity are presented. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Graduate School of Biomedical Sciences of The Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy May 2005." Approved as to style and content by: Rajesh C. Miranda, George E. Davis, David J. Earnest, James R. West, Mark J. Zoran. |
| Physical Description: | ix, 109 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 94-108). |