# Characterizing the fundamental mechanisms of epithelial invagination during ocular morphogenesis

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $385,000

## Abstract

Project Summary
Generation of the eye, more so than many organs, requires precise control of its shape for optimal function.
Obtaining knowledge of how the eye and lens is constructed during embryonic development is therefore
important to help describe the nature of ocular abnormalities that lead to major structural defects or more
subtle changes that alter vision. An example of a morphogenetic event required for the generation of organs is
epithelial invagination. This process drives the inward bending of epithelia of several early organ systems
including that of the lens placode during early ocular development. Although several mechanisms have been
proposed to drive this process, such as apical constriction or local placodal growth, none have been found
sufficient to account for epithelial bending. We have recently observed that placodal cells change shape,
move, and generate cytoskeletal structures in a planar polarized manner that produces a net flow of cells
toward the central placode. One of the hallmarks of planar-polarized cell movements such as these is the
formation and resolution of cellular rosettes, an organized process of cell rearrangement that requires spatial
restriction of junctional proteins that contract and shorten junctions and proteins that lengthen and stabilize
cellular junctions. We have identified planar-polarized localization of proteins responsible for junctional
contraction (Shroom3 and p120-catenin) and stabilization (Par3 and cdc42). These results led us to our
central hypothesis that invagination is driven by a combination of epithelial cell movements and anisotropic cell
shape changes organized by radial planar polarized protein localization, junction contraction, and junction
elongation. We will test this central hypothesis with three aims utilizing live-fluorescent microscopy of
genetically altered mouse embryos. In aim 1 we will characterize the role of anisotropic junctional contraction
and analyze the consequences of combined deficiency of Shroom3 and p120 catenin. The goal of aim 2 is to
characterize the role of Par3 in junction elongation during rosette resolution and invagination. Aim 3 will
investigate whether anisotropic cell geometry and movement results from the mutual antagonism between
proteins that induce junctional contraction and junctional elongation. Once completed, the experiments in this
proposal will define the cell behaviors that drive the mechanisms of lens placode invagination.

## Key facts

- **NIH application ID:** 9978822
- **Project number:** 5R01EY026910-05
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Timothy F Plageman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978822

## Citation

> US National Institutes of Health, RePORTER application 9978822, Characterizing the fundamental mechanisms of epithelial invagination during ocular morphogenesis (5R01EY026910-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978822. Licensed CC0.

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