# Role of Radial Glial Tiling in the Formation and Malformation of the Cerebral Cortex

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $508,567

## Abstract

Regularly interspaced, non-overlapping, tiled organization of polarized radial glial cells (RGCs)
serves as an instructive framework to generate and organize neurons in the developing cerebral
cortex. Disruptions in this fundamental cellular feature of the developing cerebral cortex lead to
a spectrum of neurodevelopmental disorders (e.g., autism, schizophrenia, and epilepsy) and
brain malformations (e.g., lissencephaly, schizencephaly, microencephaly, and
macro/microgyria). However, little is known about the molecular logic of radial glial tiling and
how it drives the appropriate formation of the cerebral cortex. We discovered that RGC tiling is
dependent on Memo1 (Mediator of cell motility 1). Genetic mutations in MEMO1 lead to autism.
Memo1 thus provides a window into the mechanisms that instruct radial glial tiling and the
resultant assembly of the cerebral cortex. Leveraging the latest advances in progenitor specific
mouse genetic models of Memo1, MADM based profiling of radial glial differentiation, mapping
of Memo1 interactome, mechanistic dissection of cellular functions of Memo1, live imaging of
Memo1 deficient radial glial cell functions, and functional analysis of MEMO1 mutation from
autism probands, we aim to (a) discover the role of Memo1 in the tiling of RGCs and the
resultant formation of the cerebral cortex, (b) identify the Memo1 interactome that contributes to
and determines RGC tiling, and (c) interrogate the contributions of MEMO1 to cortical
malformations associated with autism. Collectively, the outcome of this work will reveal the
molecular logic underlying radial glial tiling, the vital relevance of this process for cortical
development, and how changes in this process can cause brain malformations and
neurodevelopmental disorders. Importantly, understanding how radial glial cells are assembled
and organized appropriately to facilitate cerebral cortical formation offers the opportunity to
redraw the rules of corticogenesis in the service of better diagnostic and therapeutic insights
into neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 9928095
- **Project number:** 5R01HD098657-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** EVA S ANTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $508,567
- **Award type:** 5
- **Project period:** 2019-05-08 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928095

## Citation

> US National Institutes of Health, RePORTER application 9928095, Role of Radial Glial Tiling in the Formation and Malformation of the Cerebral Cortex (5R01HD098657-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9928095. Licensed CC0.

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