INTRODUCTION During development, retinal ganglion cell axons grow from the eye through the ventral diencephalon, where axons from each eye intersect, forming the optic chiasm. The optic chiasm is associated with the formation of a bilateral projection of axons

During development, retinal ganglion cell axons grow from the eye through the ventral diencephalon, where axons from each eye intersect, forming the optic chiasm. The optic chiasm is associated with the formation of a bilateral projection of axons from each retina to major visual relay nuclei (Guillery et al., 1995; Mason and Sretavan, 1997). In rodents, axons from the ventral temporal retina turn and grow to the optic tract before they reach the midline of the chiasm, forming the uncrossed projection. In contrast, axons from the nasal retina pass over the midline and form the crossed projection. The mechanisms that bring about this segregation of crossed from uncrossed axons are largely unknown. One class of molecules that has been located in the optic chiasm at appropriate developmental times, and therefore might be involved in controlling axon routings at the chiasm, are the chondroitin sulfate (CS) proteoglycans (PGs). Retinal axons are inhibited by a receding centrifugal gradient of CSPGs in the retina that may help direct growing axons to the optic nerve head (Brittis et al., 1992; Brittis and Silver, 1994). In vitro, retinal axons are inhibited by CS-PGs, which counteracts the growth-promoting effect of laminin on retinal neurite outgrowth (Snow et al., 1991; Snow and Letourneau, 1992; Dou and Levine, 1994). These results suggest an inhibitory role for CS-PGs and possible complex interactions with other adhesion systems in guiding growth of retinal axons. It has been shown in an earlier study that cells in the chiasm express CS-PGs before retinal axons arrive (Chung et al., 2000). The pattern of expression of CS-PGs is consistent with a potential inhibitory role, helping to define the course of the first axons that grow through the chiasm. Expression of CSPGs coincides with the midline glial specialization that may be responsible for preventing the uncrossed population of retinal axons from crossing (Marcus and Mason, 1995), suggesting that CS-PGs may also be involved in the control of axon divergence at the chiasm. Furthermore, in both ferret and mouse, there is a restricted expression of CS-PGs in deeper parts of the optic tract. This restricted expression of PG molecules may be responsible for deviating growing axons to the subpial region of the tract, which again suggests an inhibitory role of these molecules in controlling axon routings across this region of the pathway (Reese et al., 1997; Chung et al., 2000). 2673 Development 127, 2673-2683 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV1534