Astrocyte-encoded positional cues maintain sensorimotor circuit integrity.
Astrocyte-encoded positional cues maintain sensorimotor circuit integrity.
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星形胶质细胞是中枢神经系统中最丰富的细胞，促进突触形成并帮助完善神经连接。虽然它们在发育过程中被分配到空间上不同的区域域，但区域限制性星形胶质细胞在功能上是否异质尚不清楚。本研究表明，出生后的脊髓星形胶质细胞表达了几个区域特异性基因，腹侧星形胶质细胞编码的信号蛋白3a （Sema3a）是运动神经元和感觉神经元回路组织所必需的。星形胶质细胞编码的Sema3a缺失导致α -运动神经元轴突初始段定向失调，突触输入明显异常，α -运动神经元选择性死亡，而邻近的γ -运动神经元不发生选择性死亡。此外，TrkA+感觉传入的一个子集投射到异位的腹侧位置。这些发现表明，星形胶质细胞发育对位置线索的稳定维持影响了感觉运动回路形成的多个方面。更一般地说，他们认为区域星形胶质细胞的异质性可能有助于协调出生后神经回路的完善。
Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help 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 Semaphorin3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a led 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. Additionally, a subset of TrkA+ sensory afferents projected 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.