# Identification of gene regulatory networks controlling temporal patterning in retinal progenitor cells and neurogenic Müller glia

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $651,846

## Abstract

Project Summary:
 Over the course of developmental neurogenesis, retinal progenitor cells show progressive changes in
their ability to generate specific cell types, and become progressively more likely to undergo both neurogenic
and terminal divisions. Both intrinsic and extrinsic mechanism control these processes, which are collectively
referred to as temporal patterning. Although the identity and mechanism of action of the gene regulatory
networks that control this process has been largely unknown, we have recently used single-cell RNA-Seq and
ATAC-Seq to identify two separate transcriptional regulatory networks that respectively promote expression of
genes specifically expressed in either early or late-stage retinal progenitor cells, while repressing genes
specific to the other stage. In addition, many of these transcription factors are predicted to directly activate or
inhibit genes that regulate cell cycle progression, Notch signaling and/or neurogenesis. We propose to
determine whether these transcription factors are necessary and sufficient to control temporal profiling in
retinal progenitor cells. We will conduct both gain and loss of function analysis of transcription factors s that
are top candidates for specifying early or late-stage temporal identity, and profile resulting changes in cell
composition, gene expression, and chromatin conformation. We will then investigate the mechanism of action
of transcription factors that show clear phenotypes in further detail, determining how they regulate
developmental competence, proliferation, and neurogenesis. Finally, we will test whether gain or loss of
function of these transcription factors can reprogram neurogenic retinal Muller glia into early-stage retinal
progenitor cells. We anticipate that these studies will both identify molecular mechanisms controlling temporal
patterning in retinal progenitors, as well as new techniques for improving the directed differentiation of early-
born cell types such as retinal ganglion cells and cone photoreceptor receptors, for use in cell-based therapies
for treating blinding diseases.

## Key facts

- **NIH application ID:** 10871097
- **Project number:** 1R01EY036173-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Seth Blackshaw
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $651,846
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871097

## Citation

> US National Institutes of Health, RePORTER application 10871097, Identification of gene regulatory networks controlling temporal patterning in retinal progenitor cells and neurogenic Müller glia (1R01EY036173-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10871097. Licensed CC0.

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