# Developing a stem cell-based model to study MGE and CGE interneuron lineage specification

> **NIH NIH R03** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $81,000

## Abstract

Cortical interneurons are a diverse inhibitory neuron population in the cortex whose
dysfunction is strongly linked with neuropsychiatric illness. How diversity comes about in
interneurons is a poorly understood process. Elucidating molecular and transcriptional
mechanisms governing interneuron diversity would greatly facilitate our understanding of how
interneurons contribute to disease. It would also facilitate efforts to model neuropsychiatric
disease with human stem cell-derived neurons and help to uncover novel therapeutic avenues.
Current tools to study the molecular mechanisms driving interneuron diversity are limited in
two important aspects: 1) sample material is limited because the embryonic progenitor
domains for interneurons are small and not well-suited to applications such as biochemistry,
screening and ChIP sequencing; 2) manipulating conditions by mouse genetics is relatively low-
throughput. Objective: We therefore propose to develop a stem cell differentiation-based
model of interneuron development. Approach: It is based on an existing system that we
developed earlier but will now 1) encompass the entire interneuron lineage and has the
capacity to differentially label MGE and CGE lineages. As an initial assay to test the validity of
our new model, we will 2) examine the effects of transcriptionally-specifying both MGE and
CGE lineages with a newly-identified Wnt-Ryk signaling pathway. We recently found that Wnt-
Ryk regulates MGE interneuron identity, and this study will examine its potential role in
regulating CGE identity. Interneurons generated from this new model will be assay by in vitro
differentiation as well as by 3) in utero transplantation, which will stringently assay their
capacity to engraft, migrated and integrate with host circuitry. The proposed experiments will
allow us to definitively characterize our new in vitro model, opening the way to more expansive
studies in which a stem cell-based model serves as a powerful platform to identify molecular
and genetic pathways that govern cortical interneuron lineage specification.

## Key facts

- **NIH application ID:** 9882336
- **Project number:** 5R03MH119443-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Edmund Au
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $81,000
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9882336

## Citation

> US National Institutes of Health, RePORTER application 9882336, Developing a stem cell-based model to study MGE and CGE interneuron lineage specification (5R03MH119443-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9882336. Licensed CC0.

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