The Production of a Monoclonal Antibody That Blocks the Action of a Neurite Outgrowth-promoting Factor

Abstract

How growing axons are guided to their targets has been the subject of much speculation. A popular hypothesis is that there are macromolecules in the extracellular matrix (ECM) or on the surfaces of other cells that form pathways for axon guidance. Such molecular signals could act via a number of different mechanisms. One way of directing neurite growth is by providing a very adhesive surface for growth cone attachment (Letourneau 1975). There are, however, more elaborate ways in which such molecules could function. For instance, the extracellular signals could be recognized by surface receptors on the axons, or be internalized where they could influence the rate or direction of neurite growth. Nerve growth factor (NGF), for instance, can act as a chemoattractive agent by binding to growing neurites (Gundersen and Barrett 1980; Claude et al. 1982). A variety of cells, both non-neuronal and neuronal, might synthesize guidance molecules. Clearly, all target cells are candidates for synthesizing these factors, as was demonstrated for NGF (Ebendal et al. 1980; Korsching and Thoenen 1983). If neurons were to secrete guidance or adhesion molecules, and deposit them in an ECM along their axonal length, then these factors would be ideally localized for directing regrowth of neurites after axotomy. In addition, there is evidence that neuronal surfaces contain molecules that are adhesive for other neurites or growth cones (Rutishauser et al. 1978; Bentley and Keshishian 1982; Tagbert et al. 1982).

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