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Neuropilin-1 and neuropilin-2 bind differentially to different class 3 semaphorins and are thought to provide the ligand-binding moieties in receptor complexes mediating repulsive responses to these semaphorins. Here, we have studied the function of neuropilin-2 through analysis of a neuropilin-2 mutant mouse, which is viable and fertile. Repulsive responses of sympathetic and hippocampal neurons to Sema3F but not to Sema3A are abolished in the mutant. Marked defects are observed in the development of several cranial nerves, in the initial central projections of spinal sensory axons, and in the anterior commissure, habenulo-interpeduncular tract, and the projections of hippocampal mossyfiber axons in the infrapyramidal bundle. Our results show that neuropilin-2 is an essential component of the Sema3F receptor and identify key roles for neuropilin-2 in axon guidance in the PNS and CNS.

The coexistence of molluscan cardioexcitatory neuropeptide (FMRFAMIDE) and luteinizing hormone-releasing hormone (LHRH) was studied in the nervous system of the big brown bat, Eptesicus fuscus, with immunocytochemistry. Within mammals, this is the first report of the coexistence of these neuropeptides in the terminal nerve. In juvenile and adult bats, both neuropeptides are distributed identically throughout the terminal nerve (tn), and they coexist in many parts of the prosencephalon from the olfactory bulb as far caudally as the interpeduncular nucleus. Peripherally, on the basal surface of the forebrain, fibers and a few perikarya, which may belong to the tn, form a loose plexus. Within the brain wall, regions of maximal immunoreactivity (ir) are the habenula, medial preoptic area, arcuate nucleus, and the infundibulum. Whereas in most areas of the prosencephalon (e.g., stria terminalis and bed nuclei, amygdaloid complex) fibers show stronger immunoreactivity to FMRFAMIDE, labeling of fibers in the habenula and infundibulum is largely identical for both neuropeptides. The arcuate nucleus contains a large number of perikarya and is the major source of both FMRFAMIDE- and LHRH-ir within the forebrain. A number of fibers run along the ependyma of the ventricular system and seem to terminate here; this is particularly evident in the median eminence and infundibular stalk. In the big brown bat, there seems to exist a continuum of FMRFAMIDE- and LHRH-ir throughout the tn and those structures of the forebrain that are known to be engaged in the control of mating behavior, reproduction, and rhythmicity. Concerning the hypothalamo-hypophyseal-gonadal axis, the arcuate nucleus may serve as a central hub between the olfactory/terminal input and superior areas including the limbic system. In contrast to LHRH immunoreactivity, FMRFAMIDE-like ir extends throughout the brainstem and cervical spinal cord. This system may also be involved in the processing and modulation of autonomic input via the parabrachial and solitary nuclei, the rhombencephalic central gray, and its projection into the hypothalamus (paraventricular nucleus), thus facilitating feed-back of gonadotropic influences of the terminal nerve and prosencephalon.