| 概要： |
The connections formed between proprioceptive sensory and motor neurons provide critical sensory feedback control during locomotors. During development, proprioceptive sensory neurons project axons into the spinal cord and form both direct and indirect connections with motor neurons. Cell surface molecules in these guidance decisions remain unclear.
Semaphorins form a major family of cell surface and secreted proteins with diverse roles in the axon guidance. Semaphorins exert their developmental effects through interactions with plexin or neuropilin receptors. We identified plexinA1 as a proprioceptive axon-specific receptor, and revealed that two semas expressed by spinal cord cells, sema6C and sema6D, act as ligands for plexinA1. Analysis of plexinA1 mutant mice revealed that the loss of plexinA1 signaling elicits a dramatic defect in the positioning of proprioceptive axon shafts, which invade the dorsal horn and disrupt the organization of cutaneous sensory axons. These axonal interactions appear to be mediated by oligodendrocytes, which accompany displaced proprioceptive axon shafts into the superficial dorsal horn. Our results reveal an active program of axon shaft positioning in the mammalian CNS, and indicate that this program orchestrates the projection pattern of diverse classes of sensory neurons.
Other plexins are expressed by subsets of proprioceptive sensory neurons, raising the possibility that semaphorin-plexin signaling contributes more extensively to the establishment of sensory-motor connectivity in the spinal cord.
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