Departments of Neurobiology, Ophthalmology, and Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Departments of Neurobiology, Ophthalmology, and Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Cell Rep. 2024 Aug 27;43(8):114615. doi: 10.1016/j.celrep.2024.114615. Epub 2024 Aug 11.
In vertebrate retina, individual neurons of the same type are distributed regularly across the tissue in a pattern known as a mosaic. Establishment of mosaics during development requires cell-cell repulsion among homotypic neurons, but the mechanisms underlying this repulsion remain unknown. Here, we show that two mouse retinal cell types, OFF and ON starburst amacrine cells, establish mosaic spacing by using their dendritic arbors to repel neighboring homotypic somata. Using transgenic tools and single-cell labeling, we identify a developmental period when starburst somata are contacted by neighboring starburst dendrites; these serve to exclude somata from settling within the neighbor's dendritic territory. Dendrite-soma exclusion is mediated by MEGF10, a cell-surface molecule required for starburst mosaic patterning. Our results implicate dendrite-soma exclusion as a key mechanism underlying starburst mosaic spacing and raise the possibility that this could be a general mechanism for mosaic patterning across many cell types and species.
在脊椎动物视网膜中,同一类型的单个神经元以一种称为镶嵌的模式在组织中规则地分布。发育过程中镶嵌的建立需要同种神经元之间的细胞-细胞排斥,但这种排斥的机制仍不清楚。在这里,我们表明两种小鼠视网膜细胞类型,OFF 和 ON 星爆双极细胞,通过它们的树突来排斥相邻的同种体细胞,从而建立镶嵌间隔。使用转基因工具和单细胞标记,我们确定了星爆体细胞被相邻星爆树突接触的发育时期;这些树突用于将体细胞排除在邻居的树突领域内。树突-体细胞排斥由 MEGF10 介导,MEGF10 是星爆镶嵌模式形成所必需的细胞表面分子。我们的结果表明,树突-体细胞排斥是星爆镶嵌间隔的关键机制,并提出这种机制可能是许多细胞类型和物种镶嵌模式形成的一般机制。