# Regulation of Eye Morphogenesis

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $475,404

## Abstract

Project Summary
Congenital ocular malformations such as microphthalmia, anophthalmia and coloboma are prevalent in 1 in 3-
4,000 individuals and are the cause for over 25% of childhood blindness worldwide. Defective closure of the
optic fissure (coloboma) alone may account up to 10% of childhood blindness. Therefore, it is vitally important
to understand the molecular mechanisms underlying ocular development. While several causative genes are
identified, more effort is required to define the downstream targets and events underlying eye morphogenesis.
In our previous project, we showed that Porcn signaling needs to be tightly regulated during optic cup
formation and optic fissure closure. The Rho GTPase Cdc42 is critical for optic vesicle invagination and growth
of the optic cup, as well for optic fissure closure. Higher resolution Airyscan imaging revealed the presence of
actin-rich, filopodia-like extensions in the closing fissure. Important gaps in our understanding are how the
fissure margins make contact during the closure process and how growth of optic cup domains is coordinated.
The molecular, unconventional motor Myosin X (Myo10) can induce filopodia formation and is a novel
candidate gene for microphthalmia in humans. Our preliminary data shows that Myo10 mutant mice can exhibit
coloboma and microphthalmia. In Aim 1 of this renewal application, we propose to investigate the role of
Myo10 in ocular tissues using inducible conditional inactivation. Furthermore, the Hippo signaling pathway is a
novel key regulatory pathway controlling distinct processes during mammalian eye development. We
discovered an early role of the upstream regulator neurofibromin 2 (Nf2) in restricting retinal pigment
epithelium (RPE) proliferation in the invaginating optic cup, critical for proper optic fissure closure. In Aim 2, we
propose to examine how Nf2 disruption causes extended RPE proliferation in the early optic cup. In addition,
our preliminary data shows an early effect on ocular growth by modulation of Hippo signaling in ocular and
periocular tissues. In Aim 3, we will analyze the precise role of Yap/Taz and Nf2 during early optic cup
morphogenesis. The studies proposed here will be a critical step toward an understanding of the cellular and
molecular mechanisms controlling eye morphogenesis and important for advancing treatment and regenerative
efforts of ocular diseases.

## Key facts

- **NIH application ID:** 10931380
- **Project number:** 5R01EY024373-07
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** SABINE FUHRMANN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $475,404
- **Award type:** 5
- **Project period:** 2015-09-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931380

## Citation

> US National Institutes of Health, RePORTER application 10931380, Regulation of Eye Morphogenesis (5R01EY024373-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10931380. Licensed CC0.

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