# Cytoskeletal regulation and Yap/Taz activity in differentiating retinal neurons

> **NIH NIH R00** · CARTHAGE COLLEGE · 2020 · $248,491

## Abstract

PROJECT SUMMARY / ABSTRACT
The human retina does not regenerate after injury. This proposal examines retinal development to better
understand the molecular mechanisms that could be used to initiate regeneration. Developing neurons must
precisely regulate cytoskeletal dynamics to establish their unique morphology that is required for proper
function. It is not well understood how cytoskeletal dynamics change across development and after injury in
vivo. Yes Associated Protein (YAP) and Tafazzin (TAZ) are functionally similar proteins that are critical for
maintaining the progenitor state through transcriptional regulation. Mutations to YAP/TAZ result in retinal
lamination defects through an unknown mechanism. Additionally, unlike other retinal neurons, retinal ganglion
cells continue to express YAP/TAZ after development. Intriguingly, cytoskeletal tension can inhibit YAP/TAZ
activity and YAP/TAZ can regulate cytoskeletal dynamics. This creates an unusual molecular feedback loop
between structural proteins and transcriptional regulators. The overall goal of this proposal is to understand
the molecular mechanisms by which the cytoskeleton and YAP/TAZ coordinate retinal development, and the
role they play in retinal regeneration. The central hypothesis is that cytoskeletal rearrangements required for
retinal differentiation downregulate YAP/TAZ activity and thus drive cells out of the progenitor state. With the
knowledge gained from these studies, the ultimate goal is to reverse engineer this process in adult cells, so we
can then drive cells to a state of enhanced regenerative potential. To this end I will use a combination of
innovative in vivo imaging techniques, genetic manipulations, and regeneration assays to better understand
the molecular mechanisms by which the cytoskeleton and YAP/TAZ orchestrate retinal development and
regeneration.
The initial experiments in this proposal will focus on developing tools and techniques in zebrafish to investigate
the cytoskeleton in order to test the overall hypothesis. Mastery of the zebrafish model system is a key element
of the training potential of the K99 phase, and will complement my previous work examining retinal
development in mice. Having technical expertise in both mouse and zebrafish will enable me to answer the
most critical questions by having experimental access across retinal development, and a wide range of
molecular and genetic tools. Taken together this training plan will empower me to develop an independent line
of research that can significantly contribute to the development of regenerative therapies for the retina, and
ultimately prevent vision loss.

## Key facts

- **NIH application ID:** 9935087
- **Project number:** 5R00EY027467-05
- **Recipient organization:** CARTHAGE COLLEGE
- **Principal Investigator:** Steven J Henle
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,491
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935087

## Citation

> US National Institutes of Health, RePORTER application 9935087, Cytoskeletal regulation and Yap/Taz activity in differentiating retinal neurons (5R00EY027467-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9935087. Licensed CC0.

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