Pathfinding by retinal ganglion cell axons: transplantation studies in genetically and surgically blind mice.

Abstract

Optic axons show a highly stereotypical intracranial course to attain the visual centers of the brainstem. Here we examine the course followed by axons arising from embryonic retinae implanted in neonatal ocular retardation mutant mice in which there had been no prior innervation of the visual centers. Retinae placed on the ventrolateral brainstem adjacent to the normal site of the optic tract send axons dorsolaterally toward the ipsilateral superior colliculus, which they innervate along with a number of other subcortical visual centers. Somewhat unexpectedly, axons also course ventrally to cross at the level of the suprachiasmatic nucleus or, less frequently, caudal to the mammillary body to follow the route of the optic tract and innervate contralateral visual centers. Retinae implanted along the course of the internal capsule emit axons that follow projection fibers through the striatum to innervate the lateral geniculate nucleus and other optic nuclei. These grafts also appear to project to the lateral part of the ventrobasal nucleus of the thalamus. The results show that prior existence of an optic projection is not necessary for axons derived from ectopic retinae to attain visual nuclei, not only on the side of implantation but also on the contralateral side of the brain. The cues that these growing axons follow appear to be stable temporally. The fact that axons can also follow highly anomalous routes, such as through the internal capsule, to attain target nuclei in the brainstem suggests that the normal optic pathway is not an obligatory route for optic outgrowth.