# Identification and characterization of genes regulating zebrafish lens development

> **NIH NIH R15** · ASHLAND UNIVERSITY · 2024 · $306,457

## Abstract

PROJECT SUMMARY/ABSTRACT
The lens of the vertebrate eye becomes transparent by removing the nuclei and organelles of its
inner fiber cells. Remarkably, these fiber cells must stay alive and functional without the ability to
produce new proteins. Defects in fiber cell differentiation can contribute to lens cataract, the
leading cause of blindness worldwide. While much has been learned about the molecular
mechanisms that coordinate lens fiber cell development, there are likely many key players yet to
be discovered. Our laboratory uses the zebrafish as an efficient screening system to identify novel
genes playing a role in this process. We recently used CRISPR/Cas9 gene editing to show that
damaging the transcription factor gene, cebpg, and RNA-binding protein genes, csde1 and c1qbp,
leads to defects in lens development. Interestingly, in non-lens tissues these three genes play
roles that would be relevant to lens development, such as regulating autophagy, protein stability
and the stress response. We hypothesize that the protein products of these genes perform similar
roles in the lens. In Aim 1 of this proposal, we will characterize the spatial expression of each gene
across the developing lens of wild-type fish using RNA-scope, which detects specific mRNA
molecules. We will also detail changes in nuclear and mitochondrial loss and the elongation of fiber
cells. These experiments will allow us to identify the aspects of differentiation altered by the loss of
each gene. Aim 2 of this proposal will use RNA-Seq and RT-qPCR to detail how the lens
transcriptome is altered in each mutant. This approach will allow us to determine if the expression
of known regulators of lens fiber cell differentiation mechanisms such as autophagy, denucleation
or stress response, are changing, which would implicate them as part of the same signaling
network as our mutated genes. The transcriptomic analysis will also identify new possible
regulators of lens development, which we can then screen with our CRISPR/Cas9 system. Our
laboratory is well placed to successfully conduct these proposed experiments, which will provide
undergraduate students with excellent training in modern molecular and developmental biology
techniques and bioinformatics analysis. Our findings will take advantage of the zebrafish lens
system to address broad questions about how cells remodel during tissue differentiation.

## Key facts

- **NIH application ID:** 10794729
- **Project number:** 2R15EY013535-06
- **Recipient organization:** ASHLAND UNIVERSITY
- **Principal Investigator:** Mason Posner
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $306,457
- **Award type:** 2
- **Project period:** 2001-08-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10794729

## Citation

> US National Institutes of Health, RePORTER application 10794729, Identification and characterization of genes regulating zebrafish lens development (2R15EY013535-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10794729. Licensed CC0.

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