# Molecular mechanism of corneal epithelial stratification and innervation

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2022 · $63,562

## Abstract

PROJECT SUMMARY/ABSTRACT
Corneal epithelium (CE) is composed of a single layer of basal cells and 4-5 cell layers of non-
keratinized, stratified squamous epithelial cells to form an effective barrier against fluid loss and
pathogen. CE is mainly innervated by trigeminal sensory afferents with extremely high density,
which offers enormous sensitivity to the environmental insults for protecting otherwise deeper
ocular tissues from damage by modulating the blink response and stimulating lacrimation. Any
disruption of CE stratification and innervation can have deleterious effects on the integrity of the
cornea and lead to neurotrophic keratopathy and corneal blindness. Little is known regarding the
molecular and cellular mechanisms by which CE stratification and innervation is achieved during
corneal morphogenesis and continuously sustained in the adulthood. In this proposal, we attempt
to explore Shp2-mediated Ras–mitogen-activated protein kinase (Ras-MAPK) pathway which is
extremely important for wide variety of cellular activities and behaviors, but it has not been studied
in the CE stratification and innervation. We hypothesize that Shp2-mediated MAPK signaling
controls CE stratification and innervation via regulating ∆Np63 expression. Three aims are
proposed:
Aim 1 is to elucidate the role of Shp2→Ras→Mek→∆Np63→E-cadherin signaling pathway in
corneal epithelial stratification during and following development.
Aim 2 is to elucidate the role of Shp2→Ras→Mek→∆Np63→NGF signaling axis of the CE on the
CNV1 innervations during and following development.
Aim 3 is to rescue otherwise impaired CE stratification and innervation by overexpression of
∆Np63α in Shp2cko mice.
Completion of proposed objectives will delineate mechanistic event related to the Shp2-mediated
Ras-MAPK pathway to fine-tune ∆Np63, which in turn regulate E-cadherin and NGF, to faciliate
stratification and innervation of CE during development and in the maintenance of corneal
homeostasis. This knowledge has great potential to lead to the discovery of pathway-based
molecular target to treat corneal diseases such as neurotrophic keratopathy.

## Key facts

- **NIH application ID:** 10376207
- **Project number:** 5R01EY029071-04
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** CHIA-YANG LIU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $63,562
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-07-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376207

## Citation

> US National Institutes of Health, RePORTER application 10376207, Molecular mechanism of corneal epithelial stratification and innervation (5R01EY029071-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10376207. Licensed CC0.

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