Precocious pathfinding: retinal axons can navigate in an axonless brain.

The developing axons of retinal ganglion cells follow a stereotyped trajectory through the diencephalon to the optic tectum. In Xenopus, this trajectory closely parallels that of a preexisting fiber tract, the tract of the postoptic commissure (TPOC). This tract comprises part of the early CNS scaffold and has been proposed to play a critical role in guiding the later growing optic axons. We have tested this possibility using heterochronic and xenoplastic transplants of eye primordia to force optic axons to enter the brain before scaffold tracts have arisen in the forebrain. We show that optic axons can navigate appropriately in the absence of the TPOC or any other axons, indicating that axonal pathfinding cues are present in the axonless neuroepithelial sheet. We suggest that molecularly distinct heterogeneities within the neuroepithelium are used for pathfinding by early and late developing axons alike in normal development.