This research will examine the temporal and spatial features of the developing vestibular ganglion, hair cells and afferents. Specifically, these studies will identify gradients in phenotypic expression of proteins that characterize particular subpopulations of the ganglion cell, its afferent process and the hair cell(s) it innervates. The goal of this research is to reveal developmental mechanisms that produce this highly structured organization of the adult vestibular periphery. 1. Neurons in the vestibular ganglion undergo a temporally ordered sequence of maturation, with calretinin and substance P serving as phenotypic markers for ganglion cell populations. Temporal gradients in the development of the vestibular ganglion will be determined by pulse labeling with tritiated thymidine to determine the postmitotic dates of Scarpa's ganglion cells. Protein expression of calretinin, substance P and peripherin will be determined by standard immunohistochemical techniques. The hypothesis that calretinin positive ganglion cells undergo terminal mitosis before substance P vestibular ganglion cells will be tested. A corollary of this hypothesis i that large positive adult vestibular ganglion cells undergo terminal mitosis prior to small substance P positive ganglion cells. 2.The down-regulation of calretinin and up-regulation of calbindin expression in hair cells from central regions of the epithelium are correlated temporally with the arrival and/or morphologic maturation of calretinin positive primary afferents to the same central regions. 3.Peripherin and E-NCAM expression is restricted to hair cells and afferent units entering the peripheral regions of the epithelium. The down regulation of peripherin and E-NCAM in hair cells is correlated temporally with the arrival and/or morphological maturation of substance P/peripherin immunopositive primary afferents.
