Center for Neurobiology Research, Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, United States.
Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Blacksburg, United States.
Elife. 2022 Nov 7;11:e79833. doi: 10.7554/eLife.79833.
Axons of retinal ganglion cells (RGCs) play critical roles in the development of inhibitory circuits in visual thalamus. We previously reported that RGC axons signal astrocytes to induce the expression of fibroblast growth factor 15 (FGF15), a motogen required for GABAergic interneuron migration into visual thalamus. However, how retinal axons induce thalamic astrocytes to generate and influence interneuron migration remains unknown. Here, we demonstrate that impairing RGC activity had little impact on interneuron recruitment into mouse visual thalamus. Instead, our data show that retinal-derived sonic hedgehog (SHH) is essential for interneuron recruitment. Specifically, we show that thalamus-projecting RGCs express SHH and thalamic astrocytes generate downstream components of SHH signaling. Deletion of RGC-derived SHH leads to a significant decrease in expression, as well as in the percentage of interneurons recruited into visual thalamus. Overall, our findings identify a morphogen-dependent neuron-astrocyte signaling mechanism essential for the migration of thalamic interneurons.
视网膜神经节细胞 (RGC) 的轴突在视觉丘脑抑制性回路的发育中起着至关重要的作用。我们之前报道过,RGC 轴突向星形胶质细胞发出信号,诱导成纤维细胞生长因子 15 (FGF15) 的表达,FGF15 是一种运动因子,对于 GABA 能中间神经元迁移到视觉丘脑是必需的。然而,视网膜轴突如何诱导丘脑星形胶质细胞产生并影响中间神经元迁移仍然未知。在这里,我们证明了破坏 RGC 活性对中间神经元进入小鼠视觉丘脑的募集几乎没有影响。相反,我们的数据表明,视网膜来源的 Sonic Hedgehog (SHH) 对于中间神经元的募集是必不可少的。具体来说,我们表明投射到丘脑的 RGC 表达 SHH,并且丘脑星形胶质细胞产生 SHH 信号通路的下游成分。RGC 衍生的 SHH 的缺失导致 表达的显著减少,以及进入视觉丘脑的中间神经元的百分比减少。总的来说,我们的发现确定了一种形态发生依赖的神经元-星形胶质细胞信号机制,对于丘脑中间神经元的迁移是必不可少的。