# Clonal analysis of gliogenesis in the cerebral cortex

> **NIH NIH R56** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2021 · $532,000

## Abstract

The cerebral cortex critically relies on balanced production of neurons and glia during embryonic and early
postnatal development. Recently developed clonal lineage analysis has revealed the behavior of neural stem
cells (NSCs) giving rise to neurons in the cerebral cortex with unprecedented single-cell resolution. However,
the formation of glia by NSCs remains unclear and has yet to be systematically investigated using these new
technologies. Gliogenesis is critical for proper neuronal functions and when disrupted, it can result in various
neurological diseases. Reconstructing how glia are generated from individual NSCs and organized in the
cortex during development is essential to understand the structure-function relationships and how they can be
modulated by clone-specific factors. We have established a genetically-based single-cell lineage tracing
technique utilizing MADM (Mosaic Analysis with Double Markers) mice to label NSCs in the developing cortex
and begin to address this knowledge gap. Using this method we have found two distinct populations of glia that
occupy different territories of the cortex and its related structure the hippocampal formation. The goal of the
proposed research is to reconstruct, quantify, and mathematically model the behavior of individually labeled
NSCs in vivo. We will use the power of this labeling method to also screen for gene expression of glial clones
at single cell resolution, which all together will help us decipher the general principles organizing glial clones in
the cortex, and define how clonal siblings interact with each other. We will test the role of some of the identified
genes in generation of glial clones in the cortex, which will further help define the biological system underlying
principles of gliogenesis. Successful completion of our study will result in a comprehensive map of single NSCs
and their glial progeny in various cortical regions. Our approach will also establish a platform for detailed
quantitative and computational analysis of gliogenesis, glial diversity, and their potential for regenerative
approaches in the cortex.
Potential for Broader Impact
Our approaches to understand how important constituents of the brain, the glial cells, develop have wide
implications. Disruption of glial development is the root of a range of pathological conditions in the brain.
Therefore, understanding the basic principles and cellular mechanisms that control gliogenesis is critical to
appreciate not only how healthy development may be controlled by systematic production of glial cells, but also
how abnormalities in gliogenesis may lead to devastating neurodevelopmental disorders and brain tumors.

## Key facts

- **NIH application ID:** 10260078
- **Project number:** 1R56NS117019-01A1
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Hooman Troy Ghashghaei
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $532,000
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260078

## Citation

> US National Institutes of Health, RePORTER application 10260078, Clonal analysis of gliogenesis in the cerebral cortex (1R56NS117019-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10260078. Licensed CC0.

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