Figure 3.

Expression pattern of key molecules that direct intraretinal RGC axon guidance. RGC axons express Robo receptors and are responsive to Slit-signaling from shortly after axonogenesis. Slit1 and Slit2 present in the inner retina prevent RGC axon growth into the outer retina, helping ensure that axons extend directly into the optic fiber layer (OFL) at the inner surface of the retina. Within the optic fiber layer, the endfeet of neuroepithelial cells (glial endfeet) and cell adhesion molecules (CAMs) provide a permissive substrate. Growth of RGC axons toward the optic disk is highly directed from the outset and controlled by inhibitory gradients of Slit2 and CSPGs, highest in the retina periphery, and a centrally located attractive gradient of Shh that helps drive growth centrally (black-dashed arrows). Whether these gradients of growth-promoting and inhibitory molecules overlap within the retina or are confined to distinct domains is not known currently. Netrin-1, expressed by the optic disk glia, is essential for growth out of the eye. Inhibitory molecules, such as Slit2 and Sema5A, help restrict the RGC axons to the optic nerve once they exit the eye. In the interest of clarity, most molecules are shown only on one side of the retina but will be symmetrically distributed in vivo.