# Revealing the transcriptional and developmental mechanisms of interneuron identity

> **NIH NIH K99** · COLD SPRING HARBOR LABORATORY · 2020 · $118,421

## Abstract

Cortical GABAergic interneurons are critical components of neural circuitry, and their dysfunction has been
linked to neurodevelopmental diseases. Although the diversity of interneurons is not disputed, both the extent
of their heterogeneity and the gene regulatory mechanisms that drive it remain unclear. Recent advances in
single cell RNA-sequencing technology have shed new light on this issue, enabling the prediction of novel
interneuron subtypes based on gene expression. Cross-species meta-analysis would provide key insight into
conserved mechanisms of interneuron diversity. However, cross-study integration remains a major challenge.
I hypothesize that interneuron identity is defined by unifying molecular processes across species. This project
is designed to reveal these processes by using an integrative, cross-species approach to explore the
transcriptional, epigenetic, and developmental mechanisms that govern interneuron diversity. First, I have
shown that mouse interneuron subtypes replicably express genes associated with cell-cell communication,
enabling cross-dataset meta-analysis. The goal of Aim 1 is to use improved computational and phylogenetic
methods to define homologous interneuron subtypes across species and identify robust gene targets. Second,
preliminary investigation of single cell methylome-sequencing data indicates that it can be readily aligned with
expression data. In Aim 2 I will use machine learning methods to generate networks from epigenomic and
expression data and identify subtype-specific regulatory features. Third, I have shown that transcriptional
profiles from developing neurons can be quantitatively assessed with respect to adult expression data. Aim 3
will use meta-analytic aggregation of temporal inference methods to enable cross-dataset comparisons and
define conserved developmental gene programs. These studies will reveal a multidimensional portrait of
interneuron molecular identity and enable genetic access to these cell types, a key aim of the BRAIN Initiative.
I also propose an extensive training plan that will support my transition to independence. CSHL provides an
outstanding research environment, with unequaled opportunities for scientific discussion, advanced skills
training and career development. I have assembled an exceptional team of collaborators and mentors who will
help me to achieve my goals. Dr. Jesse Gillis, expert in transcriptome meta-analysis, and Dr. Josh Huang,
expert in GABAergic interneuron identity, will be my mentors. Dr. Bing Ren, Dr. Adam Siepel, Dr. Guoping
Feng, Dr. Jessica Tollkuhn and Dr. Michael Greenberg will be collaborators and members of my advisory
committee, ensuring that my research will be of the highest caliber. My training will also involve coursework in
multiomics data integration and comparative genomics, and I will continue my professional development by
presenting at international conferences, mentoring students and attending workshops at CSHL. Together, the
prop...

## Key facts

- **NIH application ID:** 9898481
- **Project number:** 5K99MH120050-02
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** MEGAN CROW
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $118,421
- **Award type:** 5
- **Project period:** 2019-04-01 → 2020-10-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898481

## Citation

> US National Institutes of Health, RePORTER application 9898481, Revealing the transcriptional and developmental mechanisms of interneuron identity (5K99MH120050-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9898481. Licensed CC0.

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