# Ocular complications of CHARGE Syndrome: The role of Sox11

> **NIH NIH F30** · UNIVERSITY OF KENTUCKY · 2020 · $50,035

## Abstract

Disruptions in eye development are associated with structural birth defects such as microphthalmia,
anophthalmia, and coloboma (collectively referred to as MAC), and are a significant cause of pediatric
blindness. Ocular abnormalities often occur alongside those of brain and craniofacial defects, highlighting the
significant signaling interactions between the developing structures of the head; indeed, MAC is a common
feature of systemic congenital malformation syndromes. One example is CHARGE syndrome, a genetic neural
cristopathy characterized by coloboma, heart defects, choanal atresia, growth retardation, genital
abnormalities, and ear abnormalities. Mutations in chromodomain helicase binding protein 7 (CHD7) and
defects in neural crest cell development and migration have been implicated in the pathogenesis of CHARGE
syndrome, however the mechanisms underlying the ocular birth defects observed in CHARGE patients have
not been identified.
 Our laboratory studies the development of the vertebrate visual system using zebrafish (Danio rerio).
Previous work from our lab has shown that knockdown of Sox11, a member of the SoxC family of transcription
factors, in zebrafish results in microphthalmia, coloboma, brain, trunk, and heart defects, all phenotypes
observed in CHARGE syndrome. Furthermore, we found that Sox11 is required for the expression of Bone
morphogenic proteins (BMPs) during ocular development. In humans, a duplication of Sox11 has been
identified in a patient clinically diagnosed with CHARGE syndrome, and CHD7 has been shown to directly
interact with Sox11 and Sox4 in neural stem cells. Based on these data, my central hypothesis is that the loss
of Sox 11 expression leads to disruptions in neural crest cell dynamics as well as alterations in BMP signaling
during development. This hypothesis will be tested in the following aims 1) Determine the role that Sox11 and
Chd7 play in the specification, proliferation, survival, and migration of cranial neural crest cells, and 2)
Determine whether Sox11 and Chd7 deficiency alters cranial BMP signaling. This proposal will employ
innovative and cutting edge live imaging techniques, as well as advanced biochemical and molecular biology
approaches, and will leverage the power of the zebrafish model to tackle an important problem in ocular
pediatric genetics.
 Successful completion of this project will define the role of Sox11 in the pathogenesis of the ocular
defects such as those observed in CHARGE syndrome and make progress towards improving the
identification, management, and treatment of congenital eye malformations. Additionally, this predoctoral
proposal allows the candidate to develop unique technical, critical thinking, and effective communication skills
crucial to a physician-scientist specializing in ophthalmic pediatric genetics.
!

## Key facts

- **NIH application ID:** 9987788
- **Project number:** 1F30EY031545-01
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Laura Krueger
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,035
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987788

## Citation

> US National Institutes of Health, RePORTER application 9987788, Ocular complications of CHARGE Syndrome: The role of Sox11 (1F30EY031545-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987788. Licensed CC0.

---

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