Development of the central nervous system is dependent upon precisely- timed cellular and molecular interactions between specific neural elements. If these interactions fail to take place, as in the case of birth defects or embryonic neurological disorders, a cascade of irreversible developmental problems may ensue. The thrust of this proposal is to examine cellular interactions in a brain region that is critically-dependent upon timely development of innervation by sensory afferent axons for its growth and maturation. Thus, in the African clawed frog, Xenopus laevis, we will continue our examination of the development of the olfactory bulb with particular reference to examining the effects of sensory deafferentation on the development of the olfactory bulb, including determination of the fate of differentiated mitral/tufted cells (output neurons of the bulb), volume of the bulb, number of mitral/tufted cells, and neurogenesis. We will also examine the influence of supernumerary peripheral olfactory tissue on the volume of the bulb and the number of output neurons, and the expression of developmentally-regulated genes in the olfactory bulb. We will study these issues by experimentally-manipulating the peripheral innervation through the removal of nasal capsules at different stages of development or transplantation of an extra nasal capsule so that it will innervate the olfactory bulb during early stages of larval development. Experimental approaches will make use of light and electron microscopy, cell birthdating, neuroanatomical tract-tracing, in situ hybridization, and various techniques of molecular biology. The underlying purpose of these experiments is to identify the cellular and molecular elements that are induced or controlled by sensory afferents during critical periods of development, with the ultimate goal of identifying the factors in afferent fibers that perform these functions.
