Lateral and radial growth uncoupled in reaggregated retinospheroids of embryonic avian retina.

According to an earlier resented model (Layer and Willbold, Int. Rev. Cytol. 146: 1-47, 1993), growth of the retina can be conceived of as an areal increase of an epithelial tissue sheet ("lateralization") plus a concomitant establishment of the layered retina ("radialization"). To provide further support for this model, here we have reaggregated dissociated retinal plus pigmented cells from chick or quail embryos and observed their development into histotypic three-dimensional spheres in rotation culture. These so-called stratospheroids consist of a continuous fully laminated retinal part with a coiled-up pigmented epithelial core. Using BrdU-labeling, we show that radial growth, i.e. the sequential production of cell types in spheroids, is comparable to normal vitreal-scleral retinogenesis. The region next to the pigmented epithelial core represents a "lateral growth zone" (equivalent to an ora serrata in vivo), where mitotic cell numbers are highest, even when in the laminated part proliferation has already ceased. Gradients of lateral differentiation emanate from this growth zone into the retinal tissue, as revealed by immunostaining of the photoreceptor protein opsin and the cell recognition molecule F11. Moreover, we found that stratospheroids derived from older embryos consist only of a hollow monolayered neuroepithelium which develops in the absence of any radial growth. This indicates that cell production is sustained longer in lateral than in radial direction. These differently staged stratospheroids will be excellent models to characterize genes involved in the regulation of lateral and radial growth processes.