April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Math5 Confers Multipotency to Fate-Restricted Post-Mitotic Retinal Precursors
Author Affiliations & Notes
  • L. Prasov
    Human Genetics,
    University of Michigan, Ann Arbor, Michigan
  • T. Glaser
    Internal Medicine and Human Genetics,
    University of Michigan, Ann Arbor, Michigan
  • Footnotes
    Commercial Relationships  L. Prasov, None; T. Glaser, None.
  • Footnotes
    Support  NIH grants EY14249 (TG), T32 GM07863 and T32 EY013934 (LP), and The Glaucoma Foundation (TG).
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 1310. doi:
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      L. Prasov, T. Glaser; Math5 Confers Multipotency to Fate-Restricted Post-Mitotic Retinal Precursors. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1310.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : The Math5 (Atoh7) basic helix-loop-helix transcription factor is transiently expressed during early retinal histogenesis in a subset of newly post-mitotic precursors. These form 5% of the adult retina, including the first-born cell type, the retinal ganglion cells (RGCs). Math5 is necessary, but not sufficient, for RGC development. In lineage tracing experiments, Math5+ cells develop into all 7 major retinal cell types, and only 10% become RGCs. Here, we investigate the role of Math5 as an RGC competence factor by expressing it in a wide population of fate-restricted post-mitotic retinal precursors.

Methods: : We generated Crx>Math5-ires-Cre mice using the 2.4 kb Crx promoter to express Math5 and Cre recombinase from a single bicistronic transcript. Previous Crx>Cre and Crx>lacZ studies show that Crx is normally expressed by photoreceptors and bipolar cells, beginning shortly after terminal mitosis. We examined the properties and fates of Crx>Math5+ cells at several time points during development, using the ROSA26-flox-GFP reporter.

Results: : In 4 independent Crx>Math5-ires-Cre transgenic lines, we observed lineage-labeled cells among all retinal cell types, including RGCs. In these mice, Cre and endogenous Crx are co-expressed in post-mitotic cells throughout development. Despite this large-scale reassignment of fates, involving 90% of the neural retina, RGCs are produced in normal abundance and have birthdates before P1. Adult photoreceptor and bipolar cells continue to express Math5, but the retinal histology appears normal.

Conclusions: : Math5 can restore multipotency to fate-restricted post-mitotic retinal precursors. These cells exhibit greater plasticity than previously thought. Our results highlight the robust homeostatic mechanisms that ensure the proper ratio of cell types during retinal development.

Keywords: retinal development • ganglion cells • photoreceptors 

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