# Genetic Control of Basal Telencephalic Development

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $601,908

## Abstract

Telencephalic GABAergic neurons have central roles in cognition, movement and emotion. Dysfunction of
these neurons is implicated in epilepsy, intellectual deficiency, autism and schizophrenia. During development,
medial ganglionic eminence (MGE) progenitors generate a diversity of GABAergic neurons including
Somatostatin (SST+) and Parvalbumin (PV+) cortical interneurons (CINs), and basal ganglia projection
neurons. The identities of MGE-derived neurons are determined by the location within the MGE progenitor
domain where they are specified, and the time during development when they are produced. Understanding
the transcriptional networks that govern spatial and temporal specification is crucial for determining the basic
mechanisms of telencephalic GABAergic development, and how dysfunction of these networks can contribute
to neuropsychiatric disorders. To elucidate the transcriptional networks driving the development of MGE
progenitors and their derivatives, we must define the transcription factors (TFs) and regulatory elements (REs)
involved, as well as the coding regions that they control.
 We hypothesize that spatially and temporally specific transcriptional circuits control telencephalic
GABAergic neuron diversity. We propose a combination of genetic and genomic experiments in mice aimed at
elucidating the networks of TFs that regulate the development of neurons generated in the MGE. Our approach
leverages genetic labeling to selectively purify and manipulate specific MGE lineages, which will allow us to
integrate transcriptomic and epigenomic data. We will define RNA expression in different MGE regions and at
different ages using novel temporally-inducible CreER lines whose activities are regionally specific (Aim 1). We
will then use Histone ChIP-Seq and ATAC-Seq to identify genomic regions (candidate REs) that have spatially
and temporally dynamic epigenomic states; we will also use TF ChIP-Seq to identify in vivo binding sites for
COUPTF1/2 and MAF/MAFB (Aim 2). From these data, we will begin to uncover the transcriptional circuits
controlling MGE specification. The circuit models will be tested using mouse mutants that lack COUPTF1/2
and MAF/MAFB, TFs that we hypothesize regulate GABAergic neuron diversity in a temporal- and spatial-
dependent manner (Aim 3 & 4). Elucidating transcription circuits driving telencephalic GABAergic development
provides a fundamental framework for understanding the genetic pathways, including the REs, that generate
GABAergic neuron diversity and that may be dysregulated in neuropsychiatric disorders.

## Key facts

- **NIH application ID:** 10071919
- **Project number:** 5R01MH081880-13
- **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:** $601,908
- **Award type:** 5
- **Project period:** 2009-06-20 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071919

## Citation

> US National Institutes of Health, RePORTER application 10071919, Genetic Control of Basal Telencephalic Development (5R01MH081880-13). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071919. Licensed CC0.

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