Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.
Nat Neurosci. 2011 Jul 10;14(8):965-72. doi: 10.1038/nn.2859.
Most regions of the CNS contain many subtypes of inhibitory interneurons with specialized roles in circuit function. In the mammalian retina, the ∼30 subtypes of inhibitory interneurons called amacrine cells (ACs) are generally divided into two groups: wide/medium-field GABAergic ACs and narrow-field glycinergic ACs, which mediate lateral and vertical interactions, respectively, within the inner plexiform layer. We used expression profiling and mouse transgenic lines to identify and characterize two closely related narrow-field AC subtypes. Both arise postnatally and one is neither glycinergic nor GABAergic (nGnG). Two transcription factors selectively expressed by these subtypes, Neurod6 and special AT-rich-sequence-binding protein 2 (Satb2), regulate a postmitotic cell fate choice between these subtypes. Satb2 induces Neurod6, which persists in nGnG ACs and promotes their fate but is downregulated in the related glycinergic AC subtype. Our results support the view that cell fate decisions made in progenitors and their progeny act together to diversify ACs.
中枢神经系统的大多数区域都包含许多具有特定回路功能的抑制性中间神经元亚型。在哺乳动物视网膜中，约 30 种称为无长突细胞 (amacrine cells, ACs) 的抑制性中间神经元通常分为两类：宽/中型 GABA 能 ACs 和窄型甘氨酸能 ACs，它们分别介导内丛状层内的横向和纵向相互作用。我们使用表达谱分析和小鼠转基因系来鉴定和描述两种密切相关的窄型 AC 亚型。这两种亚型均在出生后出现，一种既不是甘氨酸能也不是 GABA 能 (nGnG)。这两种亚型选择性表达的两种转录因子，Neurod6 和富含特殊 AT 的序列结合蛋白 2 (Satb2)，调节这两种亚型之间的出生后细胞命运选择。Satb2 诱导 Neurod6 的表达，它在 nGnG ACs 中持续存在并促进其命运，但在相关的甘氨酸能 AC 亚型中下调。我们的结果支持这样的观点，即祖细胞及其后代做出的细胞命运决定共同促进 AC 的多样化。
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