June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Elucidating the molecular mechanisms underlying the coordinated differentiation of ciliary margins and neuroretina
Author Affiliations & Notes
  • Wei Liu
    Albert Einstein College of Med, Pelham, New York, United States
  • Footnotes
    Commercial Relationships   Wei Liu, None
  • Footnotes
    Support  R01EY022645, R21EY029806
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3766. doi:
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    • Get Citation

      Wei Liu; Elucidating the molecular mechanisms underlying the coordinated differentiation of ciliary margins and neuroretina. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3766.

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

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Abstract

Purpose : We aim to determine how neuroretinal differentiation and ciliary margin specification are coordinated by homeodomain transcription factors Six3 and Six6.

Methods : 1) Phenotypic analysis of Six3 and Six6 compound mutant retinas in which Six3 is conditionally deleted using Pax6 α-Cre; 2) Identification of Six3/Six6 target genes using genome-wide approaches; 3) Validation of the target genes using candidate approaches.

Results : Compound inactivation of both Six3 and Six6 in the neuroretina caused drastic retinal phenotypes. In the far peripheral regions, ciliary margins were ectopically expended at the cost of neuroretinal identity following upregulated Wnt/β-catenin signaling. In the mid-peripheral regions, the neuroretina lost its multipotency for neuroretinal differentiation. Bulk RNA sequencing identified genes downstream of Six3 and Six6 joint functions. Currently, we are investigating the molecular mechanisms underlying the region-specific phenotypes using single-cell RNA sequencing. We are also identifying Six3 occupancy in the genome using CUT&RUN. We have established procedures for eyecup culture and electroporation to functionally validate target genes.

Conclusions : Six3 and Six6 together are essential for coordinated differentiation of ciliary margins and neuroretina.

This is a 2020 ARVO Annual Meeting abstract.

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