CONTROL OF SEGMENT-SPECIFIC PREGANGLIONIC AXON OUTGROWTH

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DESCRIPTION (Applicant's Abstract): Sympathetic preganglionic neurons exhibit both an intrasegmental pattern, in which cells destined to project caudally into the sympathetic chain are located rostrally in the segment, while those that project caudally into the sympathetic chain are located caudally in the segment, and an intersegmental pattern, in which the number of rostrally or caudally projecting cells within a spinal segment is determined by the segmental position along the rostrocaudal axis. There is evidence to indicate that preganglionic cells are of two district groups, based on their pattern of projection into the sympathetic chain. First, individual cells project either rostrally or caudally into the sympathetic chain, but rarely in both directions. Second, manipulations of the periphery, such as application of exogenous retinoic acid (RA) or transposition or somites along the rostrocaudal axis, differentially alter the preganglionic cell pools. These studies have provided the first demonstration that cell proliferation and/or survival in the preganglionic cell column in the thoracic spinal cord is influenced by peripheral cues early in development. We hypothesize that preganglionic neurons have an inherent identity as either rostrally or caudally projecting cells. The specific aims of this application are designed to address when the preganglionic pools become different, what and where the molecular signals are that regulate the size of preganglionic populations, the way in which the preganglionic neurons respond to peripheral cues to make appropriate pathway choices, and what the implications of disrupting the normal regulation of pattern in this system are for the functional organization of the autonomic nervous system. The specific aims are: 1. To determine whether preganglionic neurons are fated to project either rostrally or caudally by lineage restrictions in early development. 2. To determine the way in which exogenous FGF treatment regulates the size of preganglionic populations. 3. To determine whether differential expression of receptors for extracellular matrix molecules distinguishes classes of preganglionic neuron and 4. To determine whether alterations in the number of either class of sympathetic preganglionic neurons is associated with concomitant alterations in either cell number or innervation density within the paravertebral sympathetic chain ganglia. Understanding the regulation of the organization of this system has the potential to provide a unique situation for studying the general way in which topographic maps of the body are matched to various levels of the neuraxis.