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Wei Liu, Raven Diacou, Ales Cvekl; Six3 and Six6 are required for protecting multipotent retinal progenitors against ciliary margin fate through suppressing Wnt/β-catenin signaling. Invest. Ophthalmol. Vis. Sci. 2018;59(9):582. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the molecular mechanisms underlying retinal differentiation.
Molecular characterization of the mutant retinas in which Six3 was conditionally deleted at E10.5 in combination with Six6-deletion.
Through characterization of the retinas in which homeobox gene Six3 was deleted at E10.5 in Six6-null background (DKO), we demonstrate synergistic Six3 and Six6 functions are required for protecting NR progenitors against ciliary margin (CM) cell fate and for the multipotency of NR progenitors. DKO retinas displayed drastic phenotypes not seen in either Six3-null or Six6-null retinas. Axin2 is a readout of Wnt/β-catenin signaling, and Otx1 is a CM marker. In peripheral DKO retinas, Axin2 and Otx1 were expanded, whereas NR progenitor markers Sox2, Shh/Gli1, Notch1/Hes5, Ascl1, Atoh7, Brn3b, and Otx2 were absent or severely reduced, indicating the gain of CM identity at a cost of NR progenitor identity. In mid peripheral DKO retinas, multilineage differentiation was defective.
Thus, Six3 and Six6 suppress Wnt/β-catenin signaling and maintain the expression of multiple retinogenic factors to protect multipotent NR progenitors.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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