Publication Date:
2014-04-30
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057936/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057936/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Molofsky, Anna V -- Kelley, Kevin W -- Tsai, Hui-Hsin -- Redmond, Stephanie A -- Chang, Sandra M -- Madireddy, Lohith -- Chan, Jonah R -- Baranzini, Sergio E -- Ullian, Erik M -- Rowitch, David H -- 1DP2OD006507-01/OD/NIH HHS/ -- 5T32MH089920-04/MH/NIMH NIH HHS/ -- F31 NS081905/NS/NINDS NIH HHS/ -- R01 MH099595/MH/NIMH NIH HHS/ -- R01 NS059893/NS/NINDS NIH HHS/ -- R01 NS062796/NS/NINDS NIH HHS/ -- R01MH099595-01/MH/NIMH NIH HHS/ -- T32 GM007618/GM/NIGMS NIH HHS/ -- T32 MH089920/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 8;509(7499):189-94. doi: 10.1038/nature13161. Epub 2014 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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. ; 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]. ; 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]. ; 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. ; 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. ; Department of Neurology, University of California San Francisco, San Francisco, California 94143, USA. ; Department of Ophthalmology, University of California San Francisco, San Francisco, California 94143, USA. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24776795" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Astrocytes/cytology/*physiology
;
Axons/physiology
;
Cell Polarity
;
Cell Survival/drug effects
;
Humans
;
Mice
;
Motor Neurons/cytology/drug effects/*physiology
;
Neural Pathways/*physiology
;
Semaphorin-3A/deficiency/genetics/metabolism/pharmacology
;
Sensory Receptor Cells/cytology/*physiology
;
Spinal Cord/cytology
;
Synapses/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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