Fig. 6. Model of interaction among Notch pathway, proneural genes and cell cycle regulation in the Xenopus retinal development. (A,B) The spatial development of retinal cells in the CMZ (A) and the temporal development of retinal cells (B). (1) Stem cells divide slowly with low level of cell cycle activators; (2) retinoblasts divide rapidly as cell cycle activators rise; (3) as cell cycle activators are downregulated, retinoblasts enter their last cell cycles; (4) as expression of proneural genes of the atonal family rise in the presence of Notch, the first cells exit the cell cycle and acquire early neural fates; (5) later neural fates are the result of progressive cell cycle exit and the effect of the Notch pathway on specific proneural genes; (6) in the last phase of generating retinal cells, proneural gene expression has decreased while p27Xic1 expression has increased, favouring a glial fate. (C) Interaction models showing how the same network produces neurons when Notch and proneural levels are high (left), and glia when Notch and p27Xic1 levels are high (right).
