# Cis-regulatory circuitry underlying hedgehog mediated limb development

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $347,662

## Abstract

Abstract:
The Hedgehog (Hh) signaling pathway is a major regulator of organ development that utilizes the primary
cilium to regulate its transcriptional output through the GLI transcription factors. The effects of Hh signaling
are primarily mediated through de-repression of GLI target genes, which in the absence of Hh inhibit
transcription through an unknown mechanism. This proposal seeks to understand how GLI repressors
regulate Hedgehog signaling in normal development and how this is altered in ciliopathies. We hypothesize
that GLI repressors inhibit gene expression by regulating chromatin modifications at enhancers. We will
determine if GLI repression occurs through the recruitment of a Histone deacetylase complex. We will also
establish when GLI enhancers first acquire accessible chromatin and if their interactions with promoters
require Hh signaling. We further hypothesize that GLI proteins repress enhancer activity prior to Hh
activation. By testing this, we will provide the first detailed information about the early Hh morphogen
response and determine if GLI transcriptional dynamics are altered in a mouse model of human ciliopathies.
Collectively, these aims will provide key insights into the processes and temporal dynamics by which GLI
proteins interact with and regulate chromatin to repress transcription. In addition, they will determine how
GLI transcriptional networks are first established and altered in ciliopathies, providing insight into how GLI
dysregulation causes structural birth defects in these syndromes.

## Key facts

- **NIH application ID:** 9974352
- **Project number:** 5R01HD073151-08
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Steven Alexander Vokes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $347,662
- **Award type:** 5
- **Project period:** 2012-08-25 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974352

## Citation

> US National Institutes of Health, RePORTER application 9974352, Cis-regulatory circuitry underlying hedgehog mediated limb development (5R01HD073151-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9974352. Licensed CC0.

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