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Intrinsically different retinal progenitor cells produce specific types of progeny

Abstract

Lineage studies conducted in the retina more than 25 years ago demonstrated the multipotency of retinal progenitor cells (RPCs). The number and types of cells produced by individual RPCs, even from a single time point in development, were found to be highly variable. This raised the question of whether this variability was due to intrinsic differences among RPCs or to extrinsic and/or stochastic effects on equivalent RPCs or their progeny. Newer lineage studies that have made use of molecular markers of RPCs, retrovirus-mediated lineage analyses of specific RPCs and live imaging have begun to provide answers to this question. RPCs that produce two postmitotic daughter cells — that is, terminally dividing RPCs — have been the most well characterized RPCs to date, and have been shown to produce specific types of daughter cells. In addition, recent studies have begun to shed light on the mechanisms that drive the temporal order in which retinal cells are born.

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Figure 1: Retinal cell types and their birth order.
Figure 2: Models of retinal cell fate determination.
Figure 3: Bias in the types of neurons produced by specific RPCs.
Figure 4: Potential parallels between the development of the vertebrate retina and that of the Drosophila melanogaster CNS.

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Acknowledgements

I am grateful for helpful discussions and suggestions on the manuscript from S. Lapan, W. You, E. Guo, S. Blackshaw and M. Dyer. R. Born is gratefully acknowledged for teaching me Matlab and helping to write the simulations on clone compositions. Support from the HHMI and the NEI are also gratefully acknowledged.

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Correspondence to Connie Cepko.

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Supplementary information

Supplementary information S1 (table)

Distribution of horizontal cell subtypes in large clones in the chick retina. (PDF 159 kb)

Supplementary information S2 (figure)

Stochastic and determined mechanisms in the postnatal rat retina. (PDF 268 kb)

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Glossary

Direction-selective RGCs

(Direction-selective retinal ganglion cells). Cells that fire action potentials in response to motion in particular directions within the visual field.

Ommatidia

The basic unit of the retina of some invertebrates, consisting of a repeated pattern of photoreceptor cells that express particular opsin genes and have specific projection patterns into the brain.

Opsin

A membrane-bound G protein-coupled receptor, which is found in rod and cone photoreceptors, that initiates phototransduction. Its spectral sensitivity depends on the sequence of amino acids that tune the activity of the small chromophore, 11-cis-retinal.

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Cepko, C. Intrinsically different retinal progenitor cells produce specific types of progeny. Nat Rev Neurosci 15, 615–627 (2014). https://doi.org/10.1038/nrn3767

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