There is increasing interest in the role of RNA-binding proteins during neural development. Drosophila Musashi is one of the neural RNA-binding proteins essential for neural development and required for asymmetric cell divisions in the Drosophila adult sensory organ development. Here, a novel mammalian neural RNA-binding protein, mouse-Musashi-1, was identified based on the homology to Drosophila Musashi and Xenopus NRP-1. In the developing CNS, mouse-Musashi-1 protein was highly enriched in the CNS stem cell. Single-cell culture experiments indicated that mouse-Musashi-1 expression is associated with neural precursor cells that are capable of generating neurons and glia. In contrast, in fully differentiated neuronal and glial cells mouse-Musashi-1 expression is lost. This expression pattern of mouse-Musashi-1 is complementary to that of another mammalian neural RNA-binding protein, Hu (a mammalian homologue of a Drosophila neuronal RNA-binding protein Elav), that is expressed in postmitotic neurons within the CNS. In vitro studies indicated that mouse-Musashi-1 possesses binding preferences on poly(G) RNA homopolymer, whereas Hu is known to preferentially bind to short A/U-rich regions in RNA. Based on their differential expression patterns and distinct preferential target RNA sequences, we believe that the mouse-Musashi-1 and Hu proteins may play distinct roles in neurogenesis, either through sequential regulatory mechanisms or differential sorting of mRNA populations during asymmetric division of neural precursor cells.

Neurotransmitters such as serotonin (5HT) may have nontransmitter, trophic-like functions in the developing and adult nervous system. In order to examine this possibility in the avian spinal cord, we have quantified synapse numbers on spinal neurons following treatment with drugs that result in the destruction of 5HT positive axons. Either p-chlorophenylalanine or reserpine was injected into newly hatched or adult chickens. Following treatment for 7 days the density of nonserotoninergic synapses was considerably decreased in the targets of 5HT fibers. By contrast, neither change was observed in the dendritic structures of spinal motoneurons or in the distribution of substance P and enkephalin positive fibers. These data suggest that 5HT may play an important role in the normal increase and maintenance of synapses in developing and adult animals. A lesion of 5HT neurons may not only alter neurochemistry but also alter the general synaptic structures of the brain. While 5HT containing fibers were depleted in a dose-dependent fashion we cannot rule out the possibility that other neurotransmitter systems were depleted at higher dose of PCPA and reserpine.

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Previous studies in our laboratory /3,17/ have demonstrated that serotonin (5-HT) appears to have a trophic-like effect in enhancing synapse formation and maintenance in both the developing and the adult central nervous system. In the present study, we focused on age-related changes in the density of the axosomatic and axodendritic synapses and the number of 5-HT-positive fibers in the chicken spinal cord, with special reference to differences between the ventral (laminae VII and IX) and the dorsal (lamina I) horn. At 1 week posthatching (PIW), a transient overproduction of synapses and 5-HT-immunoreactive fibers occurred in lamina IX; all parameters had returned to their initial levels by 1 month post-hatching (PIM). The density of synapses further decreased by about 40% between P6M and P2Y (2 years posthatching). Although the magnitude of the transient increase in lamina VII was less than that in lamina IX, the changing pattern of the synapses and the 5-HT-positive fibers was similar in both regions. In the ventral horn, thin 5-HT-positive fibers were most prominent at P1W and then decreased with development; thin 5-HT-positive fibers were still found at P6M but had almost disappeared by P2Y. By contrast, at P2Y the density of the synapses and the 5-HT-positive fibers in the dorsal horn was even higher than that of younger animals.Reduction of 5-HT levels in P2Y-old chickens by p-chlorophenylalanine (pCPA) administration decreased the synaptic density in lamina I but not in lamina IX. The results of this study demonstrate that 5-HT-mediated synaptic plasticity is markedly different in the ventral and dorsal horns of the aged chicken. In the ventral horn, synaptic plasticity reached a maximum at about P1W, remained stable in the young-adult period, and then finally disappeared in the aged chicken. Conversely, the results suggest that in the dorsal horn, 5-HT fibers continue to mediate the trophic influence on synaptic plasticity even in the old chicken.