Astrocyte-encoded positional cues maintain sensorimotor circuit integrity

Anna V. Molofsky, Kevin W. Kelley, Hui-Hsin Tsai, Stephanie A. Redmond, Sandra M. Chang, Lohith Madireddy, Jonah R. Chan, Sergio E. Baranzini, Erik M. Ullian and David H. Rowitch ()
Additional contact information
Anna V. Molofsky: Howard Hughes Medical Institute, University of California San Francisco
Kevin W. Kelley: Howard Hughes Medical Institute, University of California San Francisco
Hui-Hsin Tsai: Howard Hughes Medical Institute, University of California San Francisco
Stephanie A. Redmond: Neuroscience Graduate Program, University of California San Francisco
Sandra M. Chang: Howard Hughes Medical Institute, University of California San Francisco
Lohith Madireddy: University of California San Francisco
Jonah R. Chan: University of California San Francisco
Sergio E. Baranzini: University of California San Francisco
Erik M. Ullian: University of California San Francisco
David H. Rowitch: Howard Hughes Medical Institute, University of California San Francisco

Nature, 2014, vol. 509, issue 7499, 189-194

Abstract: Abstract 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 α-motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of α- but not of adjacent γ-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.

Date: 2014
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DOI: 10.1038/nature13161

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