We are attempting to establish a morphological foundation for the determination of basic developmental processes involved in the contruction of nervous systems. Simultaneously we are trying to establish which developmental events (e.g., neuron generation, axon development, dendrogenesis, synaptogenesis, etc.) exhibit genetically-associated variability and which ones do not. These goals are complementary in that genetically associated variability can be used to test the generality of hypotheses regarding basic rules of neural ontogeny. The main objective of our proposed research is to determine what developmental events are related to the genetically-associated variations which we have already observed in the ontogeny of mouse spinal reflex pathways. A study of neuronal generation in this system is nearly completed. The findings of this neuron birthday study indicate that we now need to extend our investigation to include quantitative morphological studies of individual events of neuronal differentiation (e.g., growth of axons and dendrites), and to learn whether temporal phase relationships among these individual events are importantly involved in determining the efficacy with which synaptic connectivities develop in the reflex pathway. In pursuing these studies we will use a range of procedures including electron microscopy, Golgi impregnations, radioautography, radiochemistry, and retrograde peroxidase tracing methods. It is anticipated that our investigation will provide insights concerning genetic influence on the development of neural structure and function, as well as produce information necessary for the derivation of general principles of neural ontogeny. Such research can be expected to provide a fundamental background necessary for studies of abnormal human brain development.