Nerve Growth Factor (NGF) has been shown to be critical in the normal development of sympathetic and some sensory neurons, yet this dependence has also been shown to vary with respect to the stage of development. In order to gain insight as to the role of NGF during development, it is important to know a) whether other possible targets for NGF exist during development, b) when during development receptors for NGF first appear on neuronal or other targets, and c) whether various cell types might be transitory targets for NGF. The goals of the proposed project are to determine the location of possible targets for NGF throughout the body of a mammal (mouse) and to track the appearance and/or disappearance of these specific NGF receptors during both prenatal and postnatal development. In situ NGF receptors will be identified by high resolution whole body radioautography and electron microscopic radioautography following direct administration of iodinated NGF (125I-NGF) to embryos (starting with embryonic day 9) and neonates. The feasibility of this has been demonstrated by pilot studies. Previously described targets, such as sympathetic and sensory ganglia, will be examined at various stages of their development, as well as previously uninvestigated structures in the periphery (ie. neural crest derivatives including the adrenal medulla, parafollicular cells of the thyroid gland, melanocytes, extraadrenal chromaffin cells, enteric neurons, etc.) and central nervous system. Ultimately, it is anticipated that a) the responses of these """"""""newly found"""""""" targets to NGF and its antibody will be investigated, b) the possibility of using the techniques described here to map NGF receptors during injury and repair will be explored and c) information as to the sites of synthesis and storage of NGF during development will also be obtained and correlated with these data.
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