Figure 8.

Working models for neurogenesis during late retinogenesis (e.g., P3) and mature retina in an RGC-depleted environment. A, B, Radial sections showing retinal margin and pars plana of Atoh7^LacZ/+ and Atoh7^LacZ/LacZ mice at P3. Blue denotes Atoh7 expression using an anti-LacZ antibody. In the retinal margin of an RGC-depleted retina, more cells have an active Atoh7 promoter (arrows). We believe this wider expression of Atoh7 is a retinal effort to restore its missing RGCs. Green shows Pax6-positive cells. Red is propidium iodide. Elongated, cuboidal cells that are contiguous with the retinal neuroepithelium demarcate the future pars plana. Distal to the pars plana will be the ciliary body proper. Pax6 is active in the pars plana and in the retinal margin but is downregulated in the active mitotic zone (arrowheads) which is widened in a RGC-depleted retina. At and before this stage, patterns of gene expression and proliferation are similar to the CMZ of a fish retina. Our data indicated that cells in this continuously narrowing mitotic zone might retain some neurogenic potential in a mature retina. A′, B′, Same images as shown in A and B, but without the green channel to more clearly show the LacZ labeling. C, A diagram illustration representing a radial section of the mutant mouse retinas used in this study. Many cells at the planoretinal junction, represented by a single cell at metaphase, retain proliferation potential to respond the shortage of retinal ganglion cells. Newborn cells, marked with red nuclei, migrate bidirectional into the pars plana and the retina. Although a small number of cells migrated into the retina can differentiate into neurons (marked with green cytoplasm), most of them cannot survive due to lack of essential genes (Atoh7, Pou4F2). Many newborn cells survive in the pars plana and the cilia because deletion of Atoh7 and/or Pou4F2 does not affect their survival in the region. These cells, marked with orange nuclei, can migrate further into the cilia or possibly pigmented side of the ciliary epithelium and divide again.