Orike, Nina Uche; (1996) Chemorepulsion in the developing nervous system. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This work has been directed at demonstrating the existence of diffusible growth-suppressing signals which may operate during the development of the nervous system. By co-culturing explants of different brain areas I have produced evidence for the existence of at least three distinct growth-suppressing signals. Such signals could act by specifically preventing axons from innervating inappropriate territory in the central nervous system. Evidence for the creation of territorial exclusion zones by diffusible factors is novel and in conjunction with other well described mechanisms could make important contributions to understanding axon guidance and patterning within the central nervous system. Identification of diffusible inhibitors of axon growth is not only important to the basic understanding of how neural networks become organised, but may well be critical to the problem of regeneration in the adult nervous system. I have therefore carried out research on the biochemical elucidation of the inhibitory activities. I have shown that some of these are secreted differentially according to brain area, are likely to have very short half lives and have a molecular weight range between 15 and 25KDa. If endogenous inhibitors of axon growth can be identified then there are strong possibilities for generating soluble antagonists which might eventually be of clinical relevance to pathological, degenerative and traumatic conditions of the nervous system.

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