# Transcription Factor Control of Neuronal Diversity

> **NIH NIH R37** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $445,409

## Abstract

Summary
The balance between inhibitory and excitatory neurons is established early in development in a
process dominated by the interplay between the transcriptional activator PTF1A and the
repressor PRDM13 in multiple regions of the nervous system. Initial cell fate decisions that
ultimately give rise to inhibitory neurons in the dorsal spinal cord, cerebellum, and retina depend
on the early activity of these fate-specifying transcription factors (TFs). PTF1A, like other early-
acting basic helix-loop-helix (bHLH) factors, acts as a `master regulator' by triggering
downstream genetic cascades. Such TFs have profound effects by restricting progenitor
developmental potential long before the appearance of mature neurons. In the absence of
PTF1A, neural progenitors fail to generate inhibitory neurons and aberrantly assume an
excitatory neuronal fate. Thus, the spatial and temporal control of PTF1A expression controls the
formation of the inhibitory/excitatory balance in multiple neuronal circuits. In Aim 1 we will
examine the in vivo requirement for a dorsal neural tube specific enhancer for Ptf1a at the
molecular, cellular, and behavioral levels. PRDM13, a transcriptional repressor and a direct
target of PTF1A, ensures correct specification of dorsal spinal cord inhibitory neurons by
repressing genes essential for specifying the alternative excitatory neuronal fates. Because
PRDM factors can have methyltransferase activity and/or can recruit other chromatin modifying
enzymes, and PRDM13 may bind to bHLH TFs, PRDM13 may provide a molecular link between
these factors and accompanying changes in the epigenetic landscape during neuronal subtype-
specification. Indeed, PRDM13 binds many similar genomic sites as PTF1A and another bHLH
factor ASCL1. In Aims 2 and 3, we will probe PRDM13 functions in the developing nervous
system, and test the hypothesis that PRDM13 is recruited to bHLH bound sites to facilitate
repressive chromatin modifications to repress transcription through these sites.

## Key facts

- **NIH application ID:** 9899860
- **Project number:** 5R37HD091856-04
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jane E Johnson
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $445,409
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899860

## Citation

> US National Institutes of Health, RePORTER application 9899860, Transcription Factor Control of Neuronal Diversity (5R37HD091856-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899860. Licensed CC0.

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