# Cortical development and pathogenesis in DEPDC5-related epilepsies

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $408,584

## Abstract

ABSTRACT
Focal cortical dysplasia (FCD) is the most common underlying pathology in children with drug resistant
epilepsies. DEPDC5 mutations have been increasingly recognized as the most important genetic cause in
focal epilepsies with or without FCD. Using focal somatic mutagenesis approaches, we recently generated a
rodent model with pathological and electrographic signatures that are highly clinically-relevant to human FCD.
However, precisely how dysplastic cortex and seizures arise from Depdc5 mutation remains unknown. We
propose to focus on defining the underlying genetic, cellular and circuitry mechanisms contributing to
DEPDC5-related epilepsies as well as establishing the critical roles of DEPDC5 in cortical development. We
will provide conceptual insights broadly relevant to understanding mTOR-related malformation of cortical
development and epilepsies. Our central hypothesis is that DEPDC5 mutations in cortical progenitors generate
focal intrinsic epileptogenecity through its critical roles in sculpting neural and glial development, and that
inhibition of mTORC1 recruitment will restore cytoarchitectures and suppress seizures.

## Key facts

- **NIH application ID:** 10164883
- **Project number:** 5R01NS113824-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Yu Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $408,584
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164883

## Citation

> US National Institutes of Health, RePORTER application 10164883, Cortical development and pathogenesis in DEPDC5-related epilepsies (5R01NS113824-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10164883. Licensed CC0.

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