Extrinsic and intrinsic factors control the genesis of amacrine and cone cells in the rat retina

The seven major classes of cells of the vertebrate neural retina are genera ted from a pool of multipotent progenitor cells. Recent studies suggest a m odel of retinal development in which both the progenitor cells and the envi ronment change over time (Cepko, C. L., Austin, C. P., Yang, X., Alexiades, M. and Ezzeddine, D. (1996), Proc. Natl. Acad. Sci. USA 93, 589-595), We h ave utilized a reaggregate culture system to test this model. A labeled pop ulation of progenitors from the embryonic rat retina were cultured with an excess of postnatal retinal cells and then assayed for their cell fate choi ces. We found that the postnatal environment had at least two signals that affected the embryonic cells' choice of fate; one signal inhibited the prod uction of amacrine cells and a second affected the production of cone cells . No increase in cell types generated postnatally was observed. The source of the inhibitor of the amacrine cell fate appeared to be previously genera ted amacrine cells, suggesting that amacrine cell number is controlled by f eedback inhibition. The progenitor cell lost its ability to be inhibited fo r production of an amacrine cell as it entered M phase of the cell cycle. W e suggest that postmitotic cells influence progenitor cell fate decisions, but that they do so in a manner restricted by the intrinsic biases of proge nitor cells.