# Genetic Regulation of Telencephalon Development

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $740,759

## Abstract

PROJECT SUMMARY
Telencephalic GABAergic neurons in the basal ganglia and cerebral cortex have central roles in cognition and
emotion. Dysfunction of these neurons contributes to some types of epilepsy, intellectual deficiency, autism
and schizophrenia. During development, subpallial progenitors generate most of telencephalic GABAergic
neurons, including basal ganglia projections neurons and cortical interneurons6. The Dlx1,2,5&6 homeodomain
transcription factors (TF) have central roles for this process7-24. Understanding the genetic circuitry upstream
and downstream of the DLX TFs is essential for elucidating the basic mechanisms of telencephalic GABAergic
development. To elucidate the genetic circuitry driving the development and function of telencephalic
GABAergic progenitors and neurons, we must define the TFs, REs (enhancers and promoters) and the coding
regions that they control.
 We hypothesize that the DLX homeodomain (TF) are at the core of transcriptional circuits, which we
call the “Dlx Pathway”, that regulate the development of most telencephalic GABAergic neurons, including
basal ganglia projections neurons and cortical interneurons. We propose experiments aimed at elucidating the
network of TFs in the Dlx Pathway that directly regulate genes controlling development of cells generated in
the embryonic basal ganglia (ganglionic eminences, GEs). We will use chromatin immunoprecipitation followed
by whole genome sequencing (ChIP-Seq) to elucidate in vivo genomic binding sites for TFs upstream and
downstream of Dlx1&2 (Aim 1). Analysis of changes in RNA expression in the GEs of Dlx1/2 mutants (Aim 2)
will provide evidence for the genes whose expression depends on Dlx function. Histone ChIP-Seq and ATAC-
Seq (Aim 3), in conjunction with TF ChIP-Seq, will provide evidence for the locations of regulatory elements
(REs; enhancers and promoters) used by Dlx Pathway. Final we will assay RE activity using transgenic
methods (Aims 4&5). Elucidating transcription circuits driving telencephalic GABAergic development provides
a fundamental framework for understanding the genetic pathways, including the REs, which generate inhibitory
neurons.
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## Key facts

- **NIH application ID:** 10069401
- **Project number:** 5R01MH049428-29
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** JOHN L. R. RUBENSTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $740,759
- **Award type:** 5
- **Project period:** 1992-06-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10069401

## Citation

> US National Institutes of Health, RePORTER application 10069401, Genetic Regulation of Telencephalon Development (5R01MH049428-29). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10069401. Licensed CC0.

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