fields of sight in both eyes. Mice do not have a significant overlap, whereas, humans, who do, will have about 50% of RGCs cross and 50% will remain ipsilateral. Building the repulsive outline of the chiasm Once RGCs reach the chiasm, the glial cells supporting them will change from an intrafascicular to radial morphology. A group of diencephalic cells that express the cell surface antigen stage-specific embryonic antigen (SSEA)-1 and CD44 will form an inverted V-shape. They will establish the posterior aspect of the optic chiasm border. Additionally, Slit signaling is important here: Heparin sulfate proteoglycans, proteins in the ECM, will anchor the Slit morphogen at specific points in the posterior chiasm border. RGCs will begin to express Robo, the receptor for Slit, at this point, thus facilitating the repulsion. Contralateral projecting RGCs RGC axons traveling to the contralateral optic tract need to cross. Shh, expressed along the midline in the ventral diencephalon, provides a repulsive cue to prevent RGCs from crossing the midline ectopically. However, a hole is generated in this gradient, thus allowing RGCs to cross. Molecules mediating attraction include NrCAM, which is expressed by growing RGCs and the midline glia and acts along with Sema6D, mediated via the plexin-A1 receptor. VEGF-A is released from the midline directs RGCs to take a contralateral path, mediated by the neuropilin-1 (NRP1) receptor. cAMP seems to be very important in regulating the production of NRP1 protein, thus regulating the growth cones response to the VEGF-A gradient in the chiasm. Ipsilateral projecting RGCs The only component in mice projecting ipsilaterally are RGCs from the ventral-temporal crescent in the retina, and only because they express the Zic2 transcription factor. Zic2 will promote the expression of the tyrosine kinase receptor EphB1, which, through forward signaling (see review by Xu et al.) will bind to ligand ephrin B2 expressed by midline glia and be repelled to turn away from the chiasm. Some VTc RGCs will project contralaterally because they express the transcription factor Islet-2, which is a negative regulator of Zic2 production. Shh plays a key role in keeping RGC axons ipsilateral as well. Shh is expressed by the contralaterally projecting RGCs and midline glial cells. Boc, or Brother of CDO (CAM-related/downregulated by oncogenes), a co-receptor for Shh that influences Shh signaling through Ptch1, seems to mediate this repulsion, as it is only on growth cones coming from the ipsilaterally projecting RGCs. Other factors influencing