# Identifying gene regulatory networks controlling photoreceptor specification by transcriptomic and epigenomic analysis of retinal development in cone-dominant retina

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2022 · $198,547

## Abstract

Project Summary
While degeneration of cone photoreceptors is the ultimate cause of blindness in photoreceptor dystrophies,
mouse and human retinas are rod photoreceptor-dominant, a fact that has hindered progress in understanding
how cones are specified. New insight into this problem can potentially come from studying the molecular
mechanisms of photoreceptor development in mammalian species with naturally cone-dominant retinas. One
such species is the 13-lined ground squirrel (13-LGS) Ictidomys tridecemlineatus, which is endemic to the
American Midwest. The genome of 13-LGS is fully sequenced, and their developmental staging is well-
characterized and readily comparable to mouse. We propose to comprehensively profile gene expression and
chromatin accessibility during retinal neurogenesis in 13-LGS using single-cell RNA- and ATAC-Seq. We will
then use computational approaches to identify gene regulatory networks predicted to control cone
photoreceptor development in 13-LGS, and compare these with results obtained from mouse and human
retinas to identify species-specific differences in gene expression and regulation that underlie differences in the
rod:cone ratio. We will also test whether the 13-LGS orthologue of the Nrl gene, a master regulator of
photoreceptor specification, shows reduced ability to promote rod, and repress cone, development relative to
its mouse counterpart. We expect these studies will identify multiple previously unidentified genes that are
strong candidate positive and negative regulators of cone development, and can be functionally tested in future
studies. Ultimately, this may help improve protocols for directed differentiation of cone photoreceptors from
stem and progenitor cells for use in therapeutic transplantation.

## Key facts

- **NIH application ID:** 10320067
- **Project number:** 5R21EY032281-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Seth Blackshaw
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $198,547
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320067

## Citation

> US National Institutes of Health, RePORTER application 10320067, Identifying gene regulatory networks controlling photoreceptor specification by transcriptomic and epigenomic analysis of retinal development in cone-dominant retina (5R21EY032281-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10320067. Licensed CC0.

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