Neurogenesis and Specification of Retinal Ganglion Cells.

Across all species, retinal ganglion cells (RGCs) are the first retinal neurons generated during development, followed by the other retinal cell types. How are retinal progenitor cells (RPCs) able to produce these cell types in a specific and timely order? Here, we will review the different models of retinal neurogenesis proposed over the last decades as well as the extrinsic and intrinsic factors controlling it. We will then focus on the molecular mechanisms, especially the cascade of transcription factors that regulate, more specifically, RGC fate.

PlexinA2 and Sema6A are required for retinal progenitor cell migration.

In the vertebrate retina six types of neurons and one glial cell type are generated from multipotent retinal progenitor cells (RPCs) whose proliferation and differentiation are regulated by intrinsic and extrinsic factors. RPCs proliferate undergoing interkinetic nuclear migration within the neuroblastic layer, with their nuclei moving up and down along the apico-basal axis. Moreover, they only differentiate and therefore exit the cell cycle at the apical side of the neuroblastic layer.

Development of retinal layers.

A noticeable characteristic of nervous systems is the arrangement of synapses into distinct layers. Such laminae are fundamental for the spatial organisation of synaptic connections transmitting different kinds of information. A major example of this is the inner plexiform layer (IPL) of the vertebrate retina, which is subdivided into at least ten sublayers.

Spatiotemporal expression patterns of slit and robo genes in the rat brain.

Diffusible chemorepellents play a major role in guiding developing axons toward their correct targets by preventing them from entering or steering them away from certain regions. Genetic studies in Drosophila revealed a repulsive guidance system that prevents inappropriate axons from crossing the central nervous system midline; this repulsive system is mediated by the secreted extracellular matrix protein Slit and its receptors Roundabout (Robo). Three distinct slit genes (slit1, slit2, and slit3) and three distinct robo genes (robo1, robo2, rig-1) have been cloned in mammals.