Proportion of proliferative cells in the tadpole retina is increased after embryonic lesion

Little is known about the cellular mechanisms that cause some cells to stop dividing while leaving neighboring cells free to continue dividing. Such events occur during development of the Xenopus retina; all cells of the embryonic eyebud are mitotic, but by stage 37 (St 37), only cells at the ciliary margin continue to proliferate as neighboring cells become post-mitotic. The mechanisms that control these different proliferative fates remain unknown. One possibility is that total cell number regulates the initial number of proliferative cells at the ciliary margin. To test this hypothesis, we reduced the cell number by surgically removing a portion of the embryonic eyebud, including part of the prospective proliferative zone. Cell counts confirmed that the numbers of both the mitotic, undifferentiated cells and the post-mitotic, differentiated cells were reduced following the partial ablation. A regression analysis suggested that the initial number of undifferentiated cells was a fixed proportion of the total number, but that this proportion was increased by the partial ablation. This increase occurred for all stages that the partial ablation was performed, from early optic vesicle to mid optic cup stages. The proportion of undifferentiated cells was normal in sham-operated retinas, indicating that the increase in partially ablated retinas was induced by tissue removal and not by wound healing. Analyses of clones derived from single precursors, labeled with a fluorescent lineage tracer, indicated that the rate of proliferation was the same in partially ablated and sham-operated retinas. Measurements of bromodeoxyuridine incorporation directly confirmed that at the ciliary margin cell division time was unchanged after partial ablation. Our observations are most consistent with the hypothesis that the proportion of undifferentiated cells was increased because cells that would have become post-mitotic remained proliferative after the partial ablation. Furthermore, cell-cell interactions most likely play a major role in controlling the initial number of proliferative cells in the tadpole retina.