# Identification of the molecular mechanisms mediating intrinsic control of retinal progenitor competence

> **NIH NIH R00** · WASHINGTON UNIVERSITY · 2021 · $241,529

## Abstract

The specification of retinal cell types from a common, multi-potent progenitor cell occurs in an
overlapping temporal birth order. Previous studies have concluded that the selection of an
individual progenitor to undergo a terminal division, whereby at least one daughter cell exits the
cell cycle, is largely controlled cell autonomously. Therefore, it has been hypothesized that
changes in the ability of retinal progenitors to differentiate as specific retinal cell types results
from either an inherent heterogeneity of progenitors resulting in lineage biases or global
changes in gene expression across development that correspond to changes in cell fate
specification. In order to test these hypotheses, I previously characterized the transcript
expression of individual progenitors across retinal development using single-cell RNA-sequencing.
These experiments support a model in which retinal progenitors are not lineage
restricted but exhibit global changes in gene expression corresponding to progenitor cell
maturation across development. Additionally, the profiling of retinal progenitor transcriptomes
has enabled us to identify numerous candidate genes hypothesized to 1) regulate the
proliferative potential of retinal progenitors 2) confer maturation of retinal progenitors across
developmental time and 3) control the temporal specification of individual retinal cell fates. As
proof in principal, we showed that the late progenitor cell enriched NFI transcription factors
regulate both proliferative quiescence and generation of late-born cell types. The goal of these
continued studies is to identify the mechanisms by which retinal progenitor cells are selected to
undergo a terminal division and to determine if these candidate genes also impart biases in
specification of individual retinal cell fates. The function of candidate genes in the regulation of
cell cycle exit and cell fate specification will be determined through gain/loss-of-function
experiments within the developing retina through both in vivo and ex vivo electroporations and
genetic models. Mechanistic insights into candidate gene function will be performed through
protein arrays to identify interacting proteins, ChIRP-seq/ChIP-seq to examine the RNA-DNA or
protein-DNA interactions, respectively, and through reporter assays to identify the temporal
activity of cis-regulatory elements. These studies will provide import insights into the genes and
mechanisms regulating temporal cell fate specification within the developing retina, information
vital to understanding the pathogenesis of retinal dystrophies and for understanding treatment of
these diseases.

## Key facts

- **NIH application ID:** 10183259
- **Project number:** 5R00EY027844-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Brian S Clark
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $241,529
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183259

## Citation

> US National Institutes of Health, RePORTER application 10183259, Identification of the molecular mechanisms mediating intrinsic control of retinal progenitor competence (5R00EY027844-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10183259. Licensed CC0.

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