Genetic control of retinal ganglion cell genesis

Retinal ganglion cells (RGCs) are the only projection neurons in the neural retina. They receive and integrate visual signals from upstream retinal neurons in the visual circuitry and transmit them to the brain. The function of RGCs is performed by the approximately 40 RGC types projecting to various central brain targets. RGCs are the first cell type to form during retinogenesis. The specification and differentiation of the RGC lineage is a stepwise process; a hierarchical gene regulatory network controlling the RGC lineage has been identified and continues to be elaborated. Recent studies with single-cell transcriptomics have led to unprecedented new insights into their types and developmental trajectory. In this review, we summarize our current understanding of the functions and relationships of the many regulators of the specification and differentiation of the RGC lineage. We emphasize the roles of these key transcription factors and pathways in different developmental steps, including the transition from retinal progenitor cells (RPCs) to RGCs, RGC differentiation, generation of diverse RGC types, and central projection of the RGC axons. We discuss critical issues that remain to be addressed for a comprehensive understanding of these different aspects of RGC genesis and emerging technologies, including single-cell techniques, novel genetic tools and resources, and high-throughput genome editing and screening assays, which can be leveraged in future studies.