We propose to test the hypothesis that the precise temporal order of neuron production and the first come - first served principle are essential factors in assuring the development of orderly topographic nerve connections. Specifically, as to which fibers of a sender structure will reach a target site first or last and which receiver neurons will be first or last available to arriving fibers will depend not only on the temporal order of neuron production within and between structures but also on the spatial relations within and between them. Therefore, it is postulated that the first come - first served principle may take four basic forms: (i) temporo-temporal (earliest sender neurons contacting earliest receiver neurons, and vice versa); (ii) temporo-spatial (earliest sender neurons contacting nearest receiver neurons); (iii) spatio-temporal (nearest-to-earliest connections), and (iv) spatio-spatial (nearest-to-nearest connections). Three major studies will be carried out to test this hypothesis. First, we will complete the normative dating of the birth dates of neurons throughout the rat nervous system, using the new, progressively delayed cumulative labeling procedure. The structures evaluated quantitatively will include the cochlea, the eye, the dorsal root ganglia, and specific areas of the neocortex. Second, in methacrylate-embedded whole embryos we will (i) locate the neuroepithelial zones that correspond to the neurogenetic zones identified in adults with thymidine-radiography; (ii) trace the migratory paths of young neurons from the former to the latter regions; and (iii) date the outgrowth of early fiber tracts and trace their trajectories. Third, in an attempt to experimentally evaluate the operation of the first come - first served principle, HRP and other tracers will be injected into selected central and peripheral structures in embryos of different ages. These structures will include the forelimbs and hind limbs, the cervial and lumbar spinal cord, specific regions of the sensory areas and the motor area of the neocortex, the eye, and, if possible, the inner ear.
