The cellular and molecular substrates associated with the death of massive numbers of neurons in the developing visual system remain poorly characterized. One of the more distinctive neuronal populations to undergo developmental cell death is found in the subplate zone, a transient layer of the immature cerebral cortex. This population differentiates into a number of neurochemically and morphologically distinct types which form the initial intra-cortical and subcortical projections of the visual cortex and receive the first functional synaptic contacts from the dorsal lateral geniculate nucleus. Although the formation and the elimination of the subplate and its connections are likely to be of major biological significance for understanding mechanisms of cortical development, the events controlling cell death in this neuronal population are largely unknown. The first objective of the proposed studies is to provide a detailed description of the cellular and molecular interactions between the subplate neurons and geniculocortical and corticocortical axons before and during the period of cell death, using subplate-specific molecular markers and antisera against neurotrophic factors and receptors, in conjunction with anatomical techniques at the light- and electron microscopic levels. The second objective is to biochemically characterize a newly-identified antigen (SP1) expressed by the subplate cells during the period of cell death and its regulation, using monoclonal antibodies, in combination with biochemical approaches. The third objective is to define the types of cell death in the subplate. This objective will be achieved by comparing molecular properties of neurons undergoing naturally-occurring versus experimentally-induced cell death. These studies will further our understanding of the role of the subplate in formation of the visual cortex and the causes of cell death in this structure. They represent important first steps in identifying the early and specific markers for cell death in both normal development and in genetic mutations. The new information gained could also provide a rational strategy for the discovery of clinical interventions to prevent vision loss associated with acute conditions causing neuronal degeneration, such as ischemia, stroke and trauma.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29EY009749-05
Application #
2163476
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1992-08-01
Project End
1998-07-31
Budget Start
1996-08-01
Budget End
1998-07-31
Support Year
5
Fiscal Year
1996
Total Cost
Indirect Cost
Name
Wesleyan University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Middletown
State
CT
Country
United States
Zip Code
06459
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