Date of Award

1993

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cell Biology and Anatomy

College

College of Graduate Studies

First Advisor

Gregory J. Cole

Second Advisor

David T. Kurtz

Third Advisor

Barry Ledford

Abstract

The nervous system contains hundreds of different cell-types which arise in a precise temporal and spatial developmental pattern. The complex pattern of neural development is characterized by a distinct series of events, which include cell proliferation, migration, differentiation, neurite extension, and synaptagenesis (Jacobson, 1978). Proteoglycans have been implicated in being involved in many of these processes, but have been poorly characterized in the developing vertebrate nervous system (Margolis and Margolis, 1989a; 1989b; 1993; Herndon and Lander, 1989). The studies outlined in this thesis have focussed on the identification, biochemical characterization, and developmental regulation of the major proteoglycan species in the developing chick nervous system. This analysis has provided insight into the different functions mediated by nervous system HSPGs and CSPGs\KSPGs, and have enabled us to produce specific proteoglycan antisera that can be used to elucidate specific proteoglycan functions. We have also described the molecular cloning, sequence analysis, and in situ mRNA localization, of a nervous system keratan sulfate proteoglycan, claustrin. These analyses have determined that claustrin is highly homologous to the mouse MAP1B protein, and furthermore, suggest that MAP1B itself may be a keratan sulfate proteoglycan. In situ localization of claustrin mRNA during chick development has reinforced previous studies (Cole and McCabe, 1991; McCabe and Cole, 1992; McCabe et al, 1991) suggesting that claustrin may be an inhibitory growth molecule localized to many of the proposed glial barrier structures in the developing chick CNS.

Rights

All rights reserved. Copyright is held by the author.

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