Format

Send to

Choose Destination
Nature. 2014 May 8;509(7499):189-94. doi: 10.1038/nature13161. Epub 2014 Apr 28.

Astrocyte-encoded positional cues maintain sensorimotor circuit integrity.

Author information

1
1] Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA [2] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA [3] Department of Psychiatry, University of California San Francisco, San Francisco, California 94143, USA.
2
1] Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA [2] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA [3] Department of Pediatrics, University of California San Francisco, San Francisco, California 94143, USA [4] Medical Scientist Training Program, University of California San Francisco, San Francisco, California 94143, USA [5] Neuroscience Graduate Program, University of California San Francisco, San Francisco, California 94143, USA [6].
3
1] Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA [2] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA [3] Department of Pediatrics, University of California San Francisco, San Francisco, California 94143, USA [4].
4
1] Neuroscience Graduate Program, University of California San Francisco, San Francisco, California 94143, USA [2] Department of Neurology, University of California San Francisco, San Francisco, California 94143, USA.
5
1] Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA [2] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA.
6
Department of Neurology, University of California San Francisco, San Francisco, California 94143, USA.
7
Department of Ophthalmology, University of California San Francisco, San Francisco, California 94143, USA.
8
1] Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA [2] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA [3] Department of Pediatrics, University of California San Francisco, San Francisco, California 94143, USA [4] Department of Neurosurgery, University of California San Francisco, San Francisco, California 94143, USA.

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.

PMID:
24776795
PMCID:
PMC4057936
DOI:
10.1038/nature13161
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center