Evolutionary and Developmental Specialization of Foveal Cell Types in the Marmoset

Abstract

In primates, high-acuity vision is mediated by the fovea, a small specialized central region of the retina. The fovea, unique to the anthropoid lineage among mammals, undergoes notable neuronal morphological changes during postnatal maturation. However, the extent of cellular similarity across anthropoid foveas and the molecular underpinnings of foveal maturation remain unclear. Here, we used high throughput single cell RNA sequencing to profile retinal cells of the common marmoset (Callithrix jacchus), an early divergent in anthropoid evolution from humans, apes, and macaques. We generated atlases of the marmoset fovea and peripheral retina for both neonates and adults. Our comparative analysis revealed that marmosets share almost all its foveal types with both humans and macaques, highlighting a conserved cellular structure among primate foveas. Furthermore, by tracing the developmental trajectory of cell types in the foveal and peripheral retina, we found distinct maturation paths for each. In-depth analysis of gene expression differences demonstrated that cone photoreceptors and Muller glia, among others, show the greatest molecular divergence between these two regions. Utilizing single-cell ATAC-seq and gene-regulatory network inference, we uncovered distinct transcriptional regulations differentiating foveal cones from their peripheral counterparts. Further analysis of predicted ligand-receptor interactions suggested a potential role for Muller glia in supporting the maturation of foveal cones. Together, these results provide valuable insights into foveal development, structure, and evolution. Significance statementThe sharpness of our eyesight hinges on a tiny retinal region known as the fovea. The fovea is pivotal for primate vision and is susceptible to diseases like age-related macular degeneration. We studied the fovea in the marmoset-a primate with ancient evolutionary ties. Our data illustrated the cellular and molecular composition of its fovea across different developmental ages. Our findings highlighted a profound cellular consistency among marmosets, humans, and macaques, emphasizing the value of marmosets in visual research and the study of visual diseases.