# Regulating transcription of the key neural lineage driver ASCL1

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $205,000

## Abstract

The bHLH transcription factor ASCL1 (HASH1/MASH1) is essential for neuronal differentiation
and sub-type specification of multiple neuronal cell-types throughout the brain, spinal cord, and
autonomic nervous system, as well as cells in sensory systems such as the retina and olfactory
epithelia. ASCL1 function is balanced with NOTCH signaling activity to control progenitor
proliferation and differentiation. ASCL1 has also been identified as a pioneering factor and a key
component of cocktails directly reprogramming fibroblasts to neurons. With these important
functions attributed to ASCL1, and its requirement for controlled spatial and temporal
expression in vivo for viability postnatally, it is surprising how little is known about regulation of
ASCL1 gene transcription. This gap in knowledge reflects past technical challenges in
identifying and manipulating cis-regulatory elements (REs) found at large distances from the
gene of interest. REs functioning at long-distances to control key developmental genes are
being discovered using advances in technologies that can interrogate and manipulate the
spatial genome. Here we will exploit these technologies to gain much needed insights into
transcriptional control of ASCL1 using cell culture and in vivo models of neural development.
Each model has a particular strength that allows unique aspects of ASCL1 regulation to be
uncovered. Aims include identifying and testing functions of long-range REs controlling ASCL1
during neuronal differentiation in mouse (in vivo) and human (in vitro) models. Success in these
aims will provide functional non-coding regulatory sequences controlling ASCL1 expression.
This is important for future projects to identify molecular components of the signaling complexes
working through these REs to reach the goal of providing an understanding of how a key
lineage defining transcriptional regulator is controlled during development and disease.

## Key facts

- **NIH application ID:** 10322147
- **Project number:** 5R21NS120431-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jane E Johnson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $205,000
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322147

## Citation

> US National Institutes of Health, RePORTER application 10322147, Regulating transcription of the key neural lineage driver ASCL1 (5R21NS120431-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10322147. Licensed CC0.

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