Birth dates of retinal ganglion cells giving rise to the crossed and uncrossed optic projections in the mouse.

In the mouse, as in most mammals, the crossed optic projections originate from the entire extent of the retina, whereas ganglion cells giving rise to the uncrossed (ipsilateral) projection are restricted to the temporal and ventral retina. The nasal border of this bilaterally projecting region in the retina corresponds to the midline of the visual field. Here the birth dates of ipsilaterally and contralaterally projecting ganglion cells were determined by combining tritiated thymidine labelling in the embryo with horseradish peroxidase tracings from the optic tract in the adult. Contralaterally projecting ganglion cells were found to be generated from embryonic day E11 to about E19 in a crude concentric fashion with the oldest cells in central and youngest ones in peripheral retina. Ipsilaterally projecting cells were born from E11 to E16, that is, during the earlier part of the period in which the contralateral projection was born. At the earliest time of ganglion cell generation (E11-12) ipsi- and contralaterally projecting cells were born within separate retinal regions, with the future midline representation forming the border between the two zones. This distinction became lost after E13, when both ipsi- and contralaterally projecting cells were born in the bilaterally projecting region. Hence at E11-12 the retina was found to have a bipartite organization that may allow the specification of the two maps of opposite topographical polarity in which the crossed and uncrossed projections are organized. Since in the adult retina this bipartite organization is preserved only in the large ganglion cells that project to the lateral geniculate nucleus, and since large ganglion cells are known to be the earliest ones formed in the mouse, these cells may be the ones that establish the early and bilateral projections of the retina. The conclusion that the bilateral projection system in the retina reflects an early developmental programme, and not the result of competition between the two eyes at later stages, was reinforced by observing a practically normal retinal origin of ipsilateral projections in mice which had only one normal eye from the earliest stages of eye development.