Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, ROC.
Sci Rep. 2020 Oct 28;10(1):18522. doi: 10.1038/s41598-020-75581-w.
The retinal basal glia (RBG) is a group of glia that migrates from the optic stalk into the third instar larval eye disc while the photoreceptor cells (PR) are differentiating. The RBGs are grouped into three major classes based on molecular and morphological characteristics: surface glia (SG), wrapping glia (WG) and carpet glia (CG). The SGs migrate and divide. The WGs are postmitotic and wraps PR axons. The CGs have giant nucleus and extensive membrane extension that each covers half of the eye disc. In this study, we used lineage tracing methods to determine the lineage relationships among these glia subtypes and the temporal profile of the lineage decisions for RBG development. We found that the CG lineage segregated from the other RBG very early in the embryonic stage. It has been proposed that the SGs migrate under the CG membrane, which prevented SGs from contacting with the PR axons lying above the CG membrane. Upon passing the front of the CG membrane, which is slightly behind the morphogenetic furrow that marks the front of PR differentiation, the migrating SG contact the nascent PR axon, which in turn release FGF to induce SGs' differentiation into WG. Interestingly, we found that SGs are equally distributed apical and basal to the CG membrane, so that the apical SGs are not prevented from contacting PR axons by CG membrane. Clonal analysis reveals that the apical and basal RBG are derived from distinct lineages determined before they enter the eye disc. Moreover, the basal SG lack the competence to respond to FGFR signaling, preventing its differentiation into WG. Our findings suggest that this novel glia-to-glia differentiation is both dependent on early lineage decision and on a yet unidentified regulatory mechanism, which can provide spatiotemporal coordination of WG differentiation with the progressive differentiation of photoreceptor neurons.
视网膜基底胶质细胞(RBG)是一组从视柄迁移到第三龄幼虫眼盘的胶质细胞,而光感受器细胞(PR)正在分化。根据分子和形态特征,RBG 可分为三类:表面胶质细胞(SG)、包裹胶质细胞(WG)和地毯胶质细胞(CG)。SG 迁移并分裂。WG 是有丝分裂后细胞,包裹 PR 轴突。CG 具有巨大的核和广泛的膜延伸,每个 CG 覆盖半个眼盘。在这项研究中,我们使用谱系追踪方法来确定这些胶质细胞亚型之间的谱系关系以及 RBG 发育中谱系决策的时间特征。我们发现 CG 谱系在胚胎阶段很早就与其他 RBG 分离。有人提出,SG 在 CG 膜下迁移,这阻止了 SG 与位于 CG 膜上方的 PR 轴突接触。在穿过 CG 膜的前沿时,CG 膜的前沿略微落后于标志 PR 分化前沿的形态发生沟,迁移的 SG 接触新生的 PR 轴突,PR 轴突反过来释放 FGF 诱导 SG 分化为 WG。有趣的是,我们发现 SG 均匀地分布在 CG 膜的顶部和底部,因此 CG 膜不会阻止顶部的 SG 与 PR 轴突接触。克隆分析表明,顶部和底部的 RBG 来源于进入眼盘之前确定的不同谱系。此外,基底 SG 缺乏对 FGFR 信号的反应能力,阻止其分化为 WG。我们的研究结果表明,这种新的胶质细胞到胶质细胞的分化既依赖于早期的谱系决定,也依赖于一个尚未确定的调节机制,该机制可以为 WG 分化与光感受器神经元的渐进分化提供时空协调。