Nature2014-06-18 3:13 PM

局部星形细胞在发育中所起作用 Astrocyte-encoded positional cues maintain sensorimotor circuit integrity

论文摘要 

星形细胞被广泛认为是中枢神经系统中突触形成的调控因子,同时最近的研究工作显示,它们在发育过程中往往会留在不同区域。过去我们不知道不同区域的星形细胞是相似的还是不同的,也不知道任何差异会怎样影响突触发育。在这项研究中,David Rowitch及同事证明,脊髓中的局部行星细胞能表达区域特异性基因,其中腹侧行星细胞编码的基因Sema3a是运动神经元回路的正确组织和典型的感觉传入投射模式所必需的。研究人员认为,这些行星细胞为维持正确的回路形成和优化提供了一个位置线索。

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.

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