Spatiotemporal gradients of cell genesis in the primate retina.

A cardinal event in the development of all brain structures is the time at which progenitor cells leave the cell cycle and begin to differentiate. We examined cell genesis in the retina of the macaque monkey (Macaca mulatta) by labeling dividing cells with radioactive thymidine ([3H]TdR) and following their fate at terminal division by virtue of their remaining radiolabeled after a long survival period. A number of distinct patterns of cell genesis were observed. The two tissues generated by the optic vesicle, the retinal pigment epithelium and neuroretina, share closely coincident temporal and spatial patterns of cell genesis, indicating that this process may be controlled by a common mechanism. Although overlapping to varying degrees, a clear sequence of genesis was revealed between specific cell types within the neuroretina: ganglion cells are generated first, followed by horizontal cells, cone photoreceptors, amacrine cells, Müller cells, bipolar cells, and, finally, rod photoreceptors. Retinal ganglion cells of differing soma diameter are born at different times-the smallest cells are generated early, the largest late, suggesting a further refined sequence of the functional classes of monkey retinal ganglion cells (first P gamma, then P beta, last P alpha). In addition, at sites where a homogeneous population of cells are crowded and stacked on top of each other (the foveola and perifovea for cones and ganglion cells, respectively) there is a vitreal-to-scleral intralaminar pattern of [3H]TdR labeled cell placement, which reflects both time of genesis and pattern of movement during foveation. These gradients suggest several scenarios for cell fate specification in the retina, many of which might not be obvious in mammals that develop more quickly and have less specialized retinal structure. Thus, data from the highly specialized and slowly developing macaque retina can help to understand visual development in humans and indicate useful avenues for future experimental studies in other species.