13-P132 Sonic Hedgehog is essential in lung branching morphogenesis

The optic chiasm is an important midline choice point where retinal ganglion cell (RGC) axons from each eye diverge to targets on both sides of the brain, setting up binocular vision. While several cues essential for guidance at the optic chiasm have been identified, it is clear other signals are required. We have begun to investigate the role of the highly related homophilic cell adhesion molecules, Down’s syndrome cell adhesion molecule (Dscam), Dscam Like1 (DscamL1), Sidekick1 (Sdk1) and Sidekick2 (Sdk2) in directing RGC axon guidance. Dscam is a key regulator of midline axon guidance in Drosophila and all 4 proteins are essential for the normal wiring of the vertebrate retina. Using in situ hybridisation we have examined the expression patterns of these genes in E12.5–E17.5 mouse embryos, the period when the optic chiasm is developing. At all ages Dscam and Sdk1 are expressed strongly in the RGC layer of the retina whereas Sdk2 is more widely distributed throughout the retina. Dscam and Sdk2 also are expressed in the region of the developing optic chiasm. Expression of Dscam borders the optic pathway whereas Sdk2 is expressed by the glia of the optic nerve and midline. The significance of these expression patterns is being investigated in vivo and in vitro. Work with Dscam KO mice shows that there are no obvious defects in RGC axon path-finding in embryos lacking the Dscam protein, however, there is evidence suggesting it may play a role in controlling RGC number and retinal organisation.