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].
Nature. 2014 May 8;509(7499):189-94. doi: 10.1038/nature13161. Epub 2014 Apr 28.
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.
星形胶质细胞是中枢神经系统中最丰富的细胞，它们促进突触形成，并有助于完善神经连接。尽管在发育过程中它们被分配到空间上不同的区域域，但尚不清楚区域限制的星形胶质细胞是否具有功能异质性。在这里，我们表明，出生后脊髓星形胶质细胞表达几种区域特异性基因，并且腹侧星形胶质细胞编码的 semaphorin 3a (Sema3a) 对于运动神经元和感觉神经元回路的正常组织是必需的。星形胶质细胞编码的 Sema3a 的缺失导致 α-运动神经元轴突起始段取向失调、明显异常的突触输入以及选择性的 α-运动神经元而非相邻 γ-运动神经元死亡。此外，TrkA(+)感觉传入的一部分投射到异位腹侧位置。这些发现表明，发育中的星形胶质细胞稳定维持位置线索会影响感觉运动回路形成的多个方面。更广泛地说，它们表明区域星形胶质细胞异质性可能有助于协调出生后神经回路的细化。
