Receptor-mediated cell suicide during neurogenesis and differentiation in the developing cerebral cortex /
The developing cerebral cortical neuroepithelium undergoes overlapping periods of neurogenesis, suicide and cell migration to establish the mature cortical plate. The present studies examine the role Fas/Apo[apoptosis]-1 and associated proteins, including Fas/Apo-1-mediators FADD and RIP and the i...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2000.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=727726151&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | The developing cerebral cortical neuroepithelium undergoes overlapping periods of neurogenesis, suicide and cell migration to establish the mature cortical plate. The present studies examine the role Fas/Apo[apoptosis]-1 and associated proteins, including Fas/Apo-1-mediators FADD and RIP and the inhibitor FLIP, in rodent cerebral cortical neurogenesis and differentiation including estrogen- and neurotrophin-mediated regulation of Fas/Apo-1-associated cell cycle/suicide. Fas/Apo-1 mRNA and protein are transiently expressed in the developing rat cerebral cortex. RIP was expressed by some Fas/Apo-1-expressing cells. FADD was undetectable in postnatal cerebral cortex. FLIP was expressed in postnatal cerebral cortex. Fas/Apo-1 expression was more ubiquitous in embryonic neuroblasts compared to in situ, suggesting that environmental milieu suppresses Fas/Apo-1 expression during differentiation. Furthermore, FADD, RIP and FLIP were expressed by subsets cortical neuroblasts. Fas/Apo-1 activation by FasL induced caspase-dependent cell death in embryonic cortical neuroblasts. The activation of Fas/Apo-1 was also accompanied by non-cell-cycle-related incorporation of nucleic acids and nuclear translocation of the RelA/p65 subunit of NF-kB. Three distinct cell phase-dependent subpopulations of cortical neuroblasts were observed during both neurogenesis and differentiation, including high and moderate Fas/Apo-1-expressing and non-Fas-expressing groups. Fas/Apo-1 intensity correlated with BrdU incorporation, though non-adherent apoptotic cells showed higher correlation than adherent, apoptotic cells. Anchorage loss accompanied increased apoptosis and uncoupling of Fas/Apo-1 expression from p53 phosphorylation and FLIP expression. Fas/Apo-1 and FADD expression remained co-regulated. Estrogen increased neurogenesis and regulated Fas/Apo-1 expression in a cell cycle- and anchorage-dependent manner. Both estrogen and Fas/Apo-1 increased the expression of cyclin A. However, following Fas/Apo-1 activation, estrogen induced a decrease in p21/Waf-1 and PCNA, without reduction in cyclin A. However, during differentiation, estrogen decreased cell survival and potentiated S-phase while attenuating G2/M whereas NT-3/BDNF increased cell survival while BDNF increased entry into cell cycle. The cytotoxic factor ethanol led to a dose-specific increase in Fas/Apo-1 expression. These findings suggest that Fas/Apo-1 and associated proteins are functionally expressed in the developing cerebral cortex and regulated by specific trophic in a developmental stage and cell-phase-specific manner. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". |
| Physical Description: | xiii, 249 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 173-246). |