Transcription factor Olig2 defines subpopulations of retinal progenitor cells biased toward specific cell fates

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 20; pp. 7882 - 7887
• Main Authors: Hafler, Brian P, Surzenko, Natalia, Beier, Kevin T, Punzo, Claudio, Trimarchi, Jeffrey M, Kong, Jennifer H, Cepko, Constance L
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15-05-2012; National Acad Sciences
• Subjects: Amacrine cells; Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biological Sciences; Cell Differentiation - physiology; Cell division; Cell Lineage - physiology; Cells; Drosophila melanogaster; Electroporation; ganglia; Gene expression; Immunohistochemistry; In Situ Hybridization; Infections; interneurons; Mice; Molecular structure; Mother cells; Multipotent stem cells; Nerve Tissue Proteins - metabolism; Neural stem cells; Neurons; Oligodendrocyte Transcription Factor 2; Progenitor cells; progeny; Proteins; Retina; Retina - cytology; rods (retina); Stem cells; Stem Cells - metabolism; transcription factors; ventral nerve cord
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1203138109

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 transcription factor, Olig2. 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 later, postnatal Olig2+ RPCs also made terminal divisions, which were biased toward production of rod photoreceptors and amacrine cell interneurons. These data indicate that the multipotent progenitor pool is made up of distinctive types of RPCs, which have biases toward 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.