The role of muscle in the development and differentiation of spinal motoneurons: in vitro studies.

Results of in vivo experiments suggest that muscle cells, and probably other cell types, produce factors upon which motoneurons depend for survival and normal development. Most attempts to characterize such factors have used cultures of enriched or identified motoneurons, and have studied effects of muscle-derived substances on survival, neurite outgrowth and acetylcholine synthesis. Results from different laboratories vary widely, both in terms of the estimated abundance of motoneurons as a fraction of total dissociated spinal cord and in terms of the molecular weight estimates for factors tentatively proposed as candidate motoneuron growth factors. Nevertheless, there are several independent reports of 40-55 kDa species affecting each of the three parameters of spinal neuron development. We have begun to characterize one of these, partially purified from extracts of denervated muscle on the basis of its neurite-promoting activity for a subpopulation of 4.5-day embryonic chicken spinal neurons. Comparison between the factors under study in different systems, and confirmation of their importance in vivo, await the preparation of specific blocking antibodies.