# Mechanisms underlying the formation of the cornea and ocular surface epithelium

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $390,851

## Abstract

The ocular surface consists of a single continuous layer of epithelium and all associated structures, including
the surface and glandular epithelia of the cornea, conjunctiva, and limbus, as well as the lacrimal and
meibomian glands. The ocular surface plays a central role in vision, and diseases and disorders of the ocular
surface and cornea is a leading cause of vision problems. The development, establishment, and maintenance
of the ocular surface depend on the precise control of genetic networks that are tightly regulated by
mesenchymal-epithelial interactions at the cellular level. Importantly, neural crest (NC)-derived cells give rise to
the corneal and eyelid mesenchyme and are crucial for formation of the ocular surface. The long-term goal of
our lab is to elucidate the fundamental mechanisms that regulate the formation and maintenance of the ocular
surface and to understand how disruption of these mechanisms lead to defects in the ocular surface and
cornea. Inactivating mutations of human FOXC2 are responsible for the autosomal dominant syndrome
Lymphedema-distichiasis, which is characterized by the obstruction of lymphatic drainage in the limbs and the
growth of aberrant, extra eyelashes (distichiasis). We have completed preliminary experiments suggesting (1)
that an NC-specific mutation of Foxc2 in mice leads to corneal conjunctivalization, ectopic corneal
neovascularization, defects in meibomian gland development, and impaired ocular epithelial cell identity, and
(2) that compound, NC-specific mutations of Foxc2 and a closely related gene, Foxc1, have more severe eye
defects, including the complete absence of the cornea, accompanied by significant declines in the expression
of another key developmental factor, Pitx2, and its downstream effector Dkk2, which antagonizes canonical
Wnt signaling. Thus, our central hypothesis is that Foxc2 is required in NC-derived cells for corneal
development and the establishment of ocular epithelial-cell identity. Guided by strong preliminary data, this
hypothesis will be tested by pursuing two specific aims: 1) Identify molecular and genetic networks that govern
corneal development; 2) Define the mechanisms by which Foxc2 participates in the formation of corneal
epithelial-cell identity. In summary, the proposed research is significant, because our findings will contribute
significantly to a better understanding of the formation of the ocular surface and the establishment of corneal
epithelial identity. This will have an important positive impact on patient care, because the completion of the
proposed studies will likely lead to identification of new targets and therapeutic strategies for improving vision
in affected patients.

## Key facts

- **NIH application ID:** 9910411
- **Project number:** 5R01EY028304-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Tsutomu Kume
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,851
- **Award type:** 5
- **Project period:** 2018-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910411

## Citation

> US National Institutes of Health, RePORTER application 9910411, Mechanisms underlying the formation of the cornea and ocular surface epithelium (5R01EY028304-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9910411. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*