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端脑和眼组织同心区的自我形成以及视网膜神经节细胞轴突的定向

Self-formation of concentric zones of telencephalic and ocular tissues and directional retinal ganglion cell axons.

作者信息

Liu Wei, Shrestha Rupendra, Lowe Albert, Zhang Xusheng, Spaeth Ludovic

机构信息

Department of Ophthalmology and Visual Sciences.

Department of Genetics.

出版信息

bioRxiv. 2023 Jun 20:2023.03.22.533827. doi: 10.1101/2023.03.22.533827.

DOI:10.1101/2023.03.22.533827
PMID:36993285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10055356/
Abstract

UNLABELLED

The telencephalon and eye in mammals are originated from adjacent fields at the anterior neural plate. Morphogenesis of these fields generates telencephalon, optic-stalk, optic-disc, and neuroretina along a spatial axis. How these telencephalic and ocular tissues are specified coordinately to ensure directional retinal ganglion cell (RGC) axon growth is unclear. Here, we report the self-formation of human telencephalon-eye organoids comprising concentric zones of telencephalic, optic-stalk, optic-disc, and neuroretinal tissues along the center-periphery axis. Initially-differentiated RGCs grew axons towards and then along a path defined by adjacent PAX2+ optic-disc cells. Single-cell RNA sequencing of CONCEPT organoids not only confirmed telencephalic and ocular identities but also identified expression signatures of early optic-disc, optic-stalk, and RGCs. These signatures were similar to those in human fetal retinas. Optic-disc cells in CONCEPT organoids differentially expressed and ; FGFR inhibitions drastically decreased RGC differentiation and directional axon growth. Through the identified RGC-specific cell-surface marker CNTN2, electrophysiologically-excitable RGCs were isolated under a native condition. Our findings provide insight into the coordinated specification of early telencephalic and ocular tissues in humans and establish resources for studying RGC-related diseases such as glaucoma.

IMPACT STATEMENT

A human telencephalon-eye organoid model that exhibited axon growth and pathfinding from retinal ganglion cell (RGC) axons is reported; via cell surface marker CNTN2 identified using scRNA-seq, early RGCs were isolated under a native condition.

摘要

未标记

哺乳动物的端脑和眼睛起源于前神经板的相邻区域。这些区域的形态发生沿着空间轴产生端脑、视柄、视盘和神经视网膜。目前尚不清楚这些端脑组织和眼组织如何协同特化，以确保视网膜神经节细胞（RGC）轴突的定向生长。在这里，我们报告了人类端脑-眼类器官的自我形成，其沿着中心-外周轴包含端脑、视柄、视盘和神经视网膜组织的同心区域。最初分化的RGC向相邻的PAX2+视盘细胞定义的路径生长轴突，然后沿着该路径生长。对概念类器官进行单细胞RNA测序，不仅证实了端脑和眼的特征，还确定了早期视盘、视柄和RGC的表达特征。这些特征与人类胎儿视网膜中的特征相似。概念类器官中的视盘细胞差异表达 和 ；FGFR抑制显著降低了RGC的分化和轴突的定向生长。通过鉴定出的RGC特异性细胞表面标记物CNTN2，在天然条件下分离出了电生理可兴奋的RGC。我们的研究结果为深入了解人类早期端脑组织和眼组织的协同特化提供了见解，并为研究青光眼等RGC相关疾病建立了资源。

影响声明

报道了一种人类端脑-眼类器官模型，该模型展示了视网膜神经节细胞（RGC）轴突的轴突生长和路径寻找；通过使用scRNA-seq鉴定的细胞表面标记物CNTN2，在天然条件下分离出了早期RGC。

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