Author
Listed:
- Anna V. Molofsky
(Howard Hughes Medical Institute, University of California San Francisco
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco
University of California San Francisco)
- Kevin W. Kelley
(Howard Hughes Medical Institute, University of California San Francisco
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco
University of California San Francisco
Medical Scientist Training Program, University of California San Francisco)
- Hui-Hsin Tsai
(Howard Hughes Medical Institute, University of California San Francisco
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco
University of California San Francisco)
- Stephanie A. Redmond
(Neuroscience Graduate Program, University of California San Francisco
University of California San Francisco)
- Sandra M. Chang
(Howard Hughes Medical Institute, University of California San Francisco
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, 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
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco
University of California San Francisco
University of California San Francisco)
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.
Suggested Citation
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 & David H. Rowitch, 2014.
"Astrocyte-encoded positional cues maintain sensorimotor circuit integrity,"
Nature, Nature, vol. 509(7499), pages 189-194, May.
Handle:
RePEc:nat:nature:v:509:y:2014:i:7499:d:10.1038_nature13161
DOI: 10.1038/nature13161
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