Date of Award

1998

Publication Type

Doctoral Thesis

Degree Name

Ph.D.

Department

Biological Sciences

Keywords

Biology, Neuroscience.

Supervisor

Zielinski, Barbara S.,

Rights

info:eu-repo/semantics/openAccess

Abstract

These studies investigated in vivo regulation of olfactory receptor neuron (ORN) axon outgrowth and guidance by molecules of the extracellular matrix (ECM). The sea lamprey olfactory system provided the opportunity for spatial-temporal examination of axonal outgrowth during ontogeny, larval development and neurogenic replacement of ORNs following an olfactory nerve axotomy. During ontogeny, acetylated tubulin (AT)-immunocytochemistry, Dil tracing and transmission electron microscopy revealed short axons that spanned the short distance between the olfactory epithelium and the primordial olfactory bulb. In larvae, the entire olfactory nerve pathway could be viewed in single horizontal sections. Lectin and Dil labeling demonstrated small ORN fascicles that emerged from the olfactory epithelium and extended to the olfactory bulb as a single olfactory nerve. Expression of proteins associated with development (GAP-43, vimentin, acetylated tubulin and NCAM) confirmed that the larval olfactory system was still developing. The role of the ECM molecule, tenascin-C was investigated during ontogeny, in larvae and perturbation studies. Although tenascin-C immunoreactivity was present in the larval olfactory nerve pathway, it was absent during ontogeny and in the larval olfactory mucosa during initial ORN outgrowth following axotomy. In both circumstances, the presence of relatively fewer ORN axons, and the short axonal pathway infer that in the absence of tenascin-C, ORN axonal fibers do not undergo extensive growth or pathway guidance. Similarly, during antibody blocking of tenascin-C in larvae, AT-immunoreactivity was diffuse. On the other hand, when tenascin levels were increased by injections following axotomy, ORN axon outgrowth of irregular-looking fascicles was stimulated. These results support previous studies of tenascin-C that demonstrated boundary signaling during axonal outgrowth. The second ECM molecule, chondroitin sulfate proteoglycan (CSPG), was localized in the nasal cartilage, lateral to the olfactory nerve pathway. The fact that the pathway turned adjacent to the cartilage, suggested CSPG may influence ORN axon outgrowth by repulsive cues. Following CSPG injections (0.33%) into olfactory-axotomized larvae, ORN axon outgrowth was deleteriously affected, suggesting that CSPG is a modulator of the olfactory nerve pathway. These studies demonstrate that the sea lamprey olfactory system is a valid in vivo model for investigating the regulation of axonal outgrowth.Dept. of Biological Sciences. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1998 .Z35. Source: Dissertation Abstracts International, Volume: 61-09, Section: B, page: 4603. Adviser: Barbara S. Zielinski. Thesis (Ph.D.)--University of Windsor (Canada), 1998.

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