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Publication : Astrocyte-encoded positional cues maintain sensorimotor circuit integrity.

First Author  Molofsky AV Year  2014
Journal  Nature Volume  509
Issue  7499 Pages  189-94
PubMed ID  24776795 Mgi Jnum  J:210605
Mgi Id  MGI:5571519 Doi  10.1038/nature13161
Citation  Molofsky AV, et al. (2014) Astrocyte-encoded positional cues maintain sensorimotor circuit integrity. Nature 509(7499):189-94
abstractText  Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help to refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded semaphorin 3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a leads to dysregulated alpha-motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of alpha- but not of adjacent gamma-motor neurons. In addition, a subset of TrkA(+) sensory afferents projects to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement.
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