# Stepwise Coordination of Eye Morphogenesis by Extracellular Matrix

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $369,813

## Abstract

Project Summary
 Developmental defects in eye structure commonly account for visual impairment in newborns. Proper eye
structure is initially established via the process of optic cup morphogenesis, during which a series of complex
cell and tissue rearrangements transforms the optic vesicle into the optic cup, with neural retina and retinal
pigmented epithelium (RPE) enwrapping the newly formed lens.
 With advances in imaging and computational analysis, work from our lab and others has begun to reveal the
cellular events underlying optic cup morphogenesis, however, molecular control of these processes still remains
poorly understood. A compelling candidate to play a role in controlling optic cup morphogenesis is the
extracellular matrix (ECM), a complex, glycoprotein-rich layer that regulates cell survival, movement, signaling,
and polarity. Mutations in certain ECM components can lead to ocular pathologies, such as coloboma,
suggesting specific requirements during optic cup morphogenesis. Understanding extrinsic control of
morphogenesis also has implications for organoid approaches and strategies. Our previous data indicate that a
core molecule, laminin, elicits diverse cellular responses in different eye regions. We also found that separate
eye domains are exposed to distinct ECM microenvironments, some of which are assembled via tissue-tissue
interactions: specifically, neural crest is required to build basement membrane around the RPE. These data
suggest that unique ECM microenvironments may be a crucial driver of regional eye morphogenetic events.
 Zebrafish provide an ideal model system to study this process: optical transparency and rapid development
offer a unique opportunity to directly observe and molecularly dissect eye formation in vivo. We previously
developed 4-dimensional imaging and computational techniques to track and visualize cell movements
throughout optic cup morphogenesis, and recently, methods for automated quantitative analysis of retinal cell
size, shape and orientation. This puts us in a unique position to analyze specific morphogenetic defects arising
when particular matrix components are disrupted. In this proposal, we will dissect the region-specific roles of
ECM factors, including nidogens, tenascin-C, mmp2, and versican, during eye morphogenesis.
 We hypothesize that dynamic, region-specific ECM microenvironments elicit unique developmental and
morphogenetic responses from distinct eye progenitor domains to drive optic cup morphogenesis. Combining
molecular genetics with innovative 4-dimensional live imaging and computational methods, we will test this
hypothesis in the following specific aims: (1) determine how ECM microenvironment controls retina
morphogenesis and organization; (2) determine how ECM modulatory factors control RPE morphogenesis; and
(3) determine functional requirements for tissue contributions to specific ECM microenvironments. The
experiments proposed will define the spatiotemporal dynamics of EC...

## Key facts

- **NIH application ID:** 10356085
- **Project number:** 5R01EY025780-06
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Kristen M Kwan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $369,813
- **Award type:** 5
- **Project period:** 2021-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356085

## Citation

> US National Institutes of Health, RePORTER application 10356085, Stepwise Coordination of Eye Morphogenesis by Extracellular Matrix (5R01EY025780-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10356085. Licensed CC0.

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