April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Ascl1 Expression Defines A Subpopulation Of Lineage-restricted Progenitors In The Mammalian Retina
Author Affiliations & Notes
  • Joseph A. Brzezinski, IV
    Department of Biological Structure, University of Washington, Seattle, Washington
  • Euiseok J. Kim
    Division of Biological Sciences, University of California at San Diego, San Diego, California
  • Jane E. Johnson
    Department of Neuroscience, UT Southwestern Medical Center, Dallas, Texas
  • Thomas A. Reh
    Department of Biological Structure, University of Washington, Seattle, Washington
  • Footnotes
    Commercial Relationships  Joseph A. Brzezinski, IV, None; Euiseok J. Kim, None; Jane E. Johnson, None; Thomas A. Reh, None
  • Footnotes
    Support  NIH Grant F32 EY19227, NIH Grant R01 EY013475, and NIH Grant R01 NS32817
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 6009. doi:
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      Joseph A. Brzezinski, IV, Euiseok J. Kim, Jane E. Johnson, Thomas A. Reh; Ascl1 Expression Defines A Subpopulation Of Lineage-restricted Progenitors In The Mammalian Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6009.

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

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Purpose: : The seven principal cell types of the neural retina derive from a population of multipotent progenitors during development. It is thought that differences in progenitor gene expression are responsible for differences in progenitor competence (potential) and subsequently, fate diversification. We investigated whether basic helix-loop-helix (bHLH) transcription factor expression heterogeneity in retinal progenitors correlated with different fate outcomes during murine retinal development.

Methods: : We assayed the expression of the bHLH transcription factors Ascl1 (Mash1), Ngn2 (Neurog2), and Olig2 in retinal progenitors using an Ascl1GFP/+ knock-in mouse line and immunohistochemistry. To determine whether progenitor transcription factor expression heterogeneity correlated with different cell fate outcomes, we conducted Ascl1 and Ngn2 inducible expression fate mapping using the CreERTM/LoxP system. We examined the number of retinal ganglion cells (RGCs) in Ascl1GFP/GFP null mice to test whether Ascl1 repressed RGC development.

Results: : We observed that progenitors were heterogeneous, expressing every possible combination of Ascl1-GFP, Ngn2, and Olig2. Lineage tracing experiments showed that Ngn2+ and Ascl1+ cells gave rise to markedly different distributions of cells. The Ngn2 lineage comprised all seven retinal cell types, whereas the Ascl1 lineage lacked a single cell type, RGCs. We also observed that Ascl1 null mice had normal numbers of RGCs during development.

Conclusions: : We show that Ascl1 expression defines a competence-restricted progenitor lineage in the retina. Nonetheless, Ascl1 itself is not required to restrict RGC competence. Our results directly correlate progenitor transcription factor expression heterogeneity with cell fate diversification during retinal development.

Keywords: transcription factors • ganglion cells • retinal development 

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