# Six1-related genes in otic development

> **NIH NIH F31** · GEORGE WASHINGTON UNIVERSITY · 2020 · $35,058

## Abstract

PROJECT SUMMARY
Nearly 120,000 babies born each year in the USA have a structural birth defect, over 30% of whom have
abnormalities in craniofacial structure. A majority of craniofacial structural anomalies stem from defects in
organs derived from the neural crest and cranial sensory placodes that often result in hearing loss. The
Branchio-oto-renal syndrome (BOR) is characterized by craniofacial and otic malformations that include the
external, middle, and/or inner ear structures. About 30% of BOS patients also have kidney defects. About half
of BOR cases have been genetically diagnosed with mutations in either the transcription factor SIX1 or its
cofactor EYA1. However, the role and regulation of Six1 transcriptional activity during different stages of ear
morphogenesis is not fully understood. Six1 plays key roles in craniofacial, otic, muscle, and kidney
development. A loss in Six1 function has been shown to reduce the expression of several cranial placode
genes and cause defects in craniofacial and otic development in zebrafish, Xenopus, chick and mouse models.
These experiments have shown that Six1 is differentially regulated during development depending on the
cofactors that form a complex with it. Additionally, mutations in known downstream targets of Six1, such as
atoh1 and sall1, also cause hearing loss. We propose to investigate the regulation and downstream effects of
Six1 transcriptional activity during key steps in inner ear morphogenesis to advance the understanding of the
role of Six1 in otic development. We will identify and functionally test proteins that complex with Six1 during
key stages of otic development (Aim 1), and genes that require Six1 activity at these developmental stages
(Aim 2). The results from the proposed work will uncover new knowledge about Six1-related genes during otic
morphogenesis. This novel information will highlight potential gene candidates to improve BOR diagnosis.

## Key facts

- **NIH application ID:** 10068505
- **Project number:** 1F31DC018742-01A1
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Aparna B. Baxi
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $35,058
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068505

## Citation

> US National Institutes of Health, RePORTER application 10068505, Six1-related genes in otic development (1F31DC018742-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10068505. Licensed CC0.

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