# CRCNS: Defining the role of astrogenesis in cortical folding

> **NIH NIH R01** · UNIVERSITY OF NOTRE DAME · 2024 · $139,958

## Abstract

Glial cells, including astrocytes, are the most prevalent cell type in the brain by far, and their dysfunctions
are known to play a role in a host of neurodevelopmental, neurodegenerative, neuroimmune, and
neuroplastic diseases and disorders. However, they have been greatly understudied relative to neurons,
and it remains unclear what role, if any, they play in cortical folding. Therefore, there is a critical need for
deeper mechanistic understanding of the role of glial cells in brain development across health and disease.
The long-term goals of the PI and co-I are to use their backgrounds, in computational mechanics and
molecular and cellular neuroscience, respectively, to understand the process of cortical folding. Here they
combine their complementary expertise to investigate the role of astrocytes in gyrification using a
combined computational-experimental approach. The overall objective of this CRCNS proposal is to relate
cellular behavior at the microscale to cerebral morphology and cortical folding at the macroscale.
In particular, we will evaluate two potential mechanisms of astrocyte proliferation: 1) that astrocytes push
on the cortex or 2) that the cortex pulls on astrocytes, causing them to grow in response. To that end, we
will experimentally manipulate and track astrocytes in the developing ferret brain using in utero
electroporation (Aim 1), develop and calibrate computational models of both mechanisms of astrocyte
behavior in cortical folding (Aim 2), and use our models to evaluate their likelihood (Aim 3). This proposal
is strongly founded on our own prior work, which has shown that astrocyte proliferation under gyri is
necessary for the formation of cortical folds in the ferret brain, and that an experimentally-calibrated
computational model can capture the dynamics of cellular behavior and the resulting tissue-level
mechanics and morphology. The combined experimental-computational approach proposed here will
contribute to our fundamental understanding of the role of glial cells in brain development, which could be
important in the study of neurodevelopmental diseases and disorders, advanced diagnostics, and effective
treatments. Furthermore, our experimentally-validated computational framework could be used to design
experimental approaches to test mechanistic hypotheses and to identify pathways for treatment in spatio- or temporally-specific events such as prenatal infection, illness, or exposure.

## Key facts

- **NIH application ID:** 10920494
- **Project number:** 5R01NS135852-02
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Maria Holland
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $139,958
- **Award type:** 5
- **Project period:** 2023-09-06 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920494

## Citation

> US National Institutes of Health, RePORTER application 10920494, CRCNS: Defining the role of astrogenesis in cortical folding (5R01NS135852-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10920494. Licensed CC0.

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