Olig2 defines subpopulations of retinal progenitor cells

Previous lineage analyses have shown that retinal progenitor cells (RPCs) are multipotent throughout development, and expression profiling studies have shown a great deal of molecular heterogeneity among RPCs. To determine if the molecular heterogeneity predicts that an RPC will produce particular types of progeny, clonal lineage analysis was used to investigate the progeny of a subset of RPCs, those that express the basic helix-loop-helix (bHLH) transcription factor, Olig2. In contrast to the large and complex set of clones generated by viral marking of random embryonic RPCs, the embryonic Olig2+ RPCs underwent terminal divisions, producing small clones with primarily two of the five cell types being made by the pool of RPCs at that time. The embryonically produced cell types made by Olig2+ RPCs were cone photoreceptors and horizontal cell (HC) interneurons. Moreover, the embryonic Olig2+ RPC did not make the later Olig2+ RPC. The later, postnatal Olig2+ RPCs also made terminal divisions, which were biased towards production of rod photoreceptors and amacrine cell (AC) interneurons. These data indicate that the multipotent progenitor pool is made up of distinctive types of RPCs, which have biases towards producing subsets of retinal neurons in a terminal division, with the types of neurons produced varying over time. This strategy is similar to that of the developing Drosophila melanogaster ventral nerve cord, with the Olig2+ cells behaving as ganglion mother cells.

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Hafler BP, Surzenko N, Beier KT, Punzo C, Trimarchi JM, Kong JH, Cepko CL