Abstract

Nogo-A is a potent inhibitor of axon regeneration that is expressed by myelin forming oligodendrocytes of the adult central nervous system (CNS). However, neuronal expression of Nogo-A during development suggests an additional role. Little is known about the putative functions of Nogo-A during embryonic development. To examine its potential role we isolated and analyzed the Nogo-A sequence in the chick, we localized its mRNA expression pattern and cell-specific distribution during key phases of cortical development, and studied regulation of its expression during phases that showed promise of function based on expression patterns.

Our results revealed five previously undescribed Nogo-A specific regions from multiple alignment of divergent species. The Nogo gene is differentially expressed during development and we identified a secondary Nogo-A splice variant. In situ hybridization found Nogo-A induction to be coincident with formation of the neural plate, the first visible structure of the CNS. Expression remained diffuse within the neuroepithelia and during later stages of cortical development (proliferation and migration) but showed an increased distribution in large projection neurons during organization of the neuronal network. In addition, we found Nogo-A to be regulated by FGF application, but not by synaptic activity. We identified evolutionarily conserved regulatory sequences surrounding the Nogo gene locus. While they did not appear to play a role in regulating gene expression during early neural development, whether they play a role in later CNS development has yet to be determined. Collectively, these data suggest Nogo-A plays a role in the determination of neural identity and/or differentiation and also appears to play a later role in the networking of large projection neurons during neurite formation and synaptogenesis.

LLU Discipline

Anatomy

Department

Anatomy

School

Graduate Studies

First Advisor

Kerby Oberg

Second Advisor

Denise Bellinger

Third Advisor

William Fletcher

Fourth Advisor

Wolff Kirsch

Fifth Advisor

Nathan Wall

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2007

Date (Title Page)

8-2007

Language

English

Library of Congress/MESH Subject Headings

Central Nervous System -- growth and development; Embryonic Development; Chick Embryo -- growth and development; Myelin Proteins; Axons.

Type

Dissertation

Page Count

xiv; 95

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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