# Establishing Common Coordinate Framework for Quantitative Cell Census in Developing Mouse Brains

> **NIH NIH RF1** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $3,797,901

## Abstract

Abstract
Brain development is characterized by a diverse set of cell types that are born and connected into rapidly growing
complex 3D structures across time. Quantitative understanding of cell type composition and distribution in
different brain regions provides fundamental knowledge about the building blocks of the brain and serves as an
essential baseline with which to assess changes that may occur in brain disorders. The importance of this
information is reflected by the significant effort among the neuroscience community, including the creation of the
BRAIN Initiative Cell Census Network, to improve our understanding of cell type compositions across different
brain regions in the adult mouse brain. These efforts have been made possible and accelerated by technological
advances in high-resolution 3D imaging coupled with computational analysis methods that can reveal cell type
arrangement in the brain with unprecedented detail. For example, we developed a quantitative brain mapping
method to uncover the spatial arrangement of GABAergic neuron subtypes in the adult mouse brain. For the
adult mouse brain, the Allen Common Coordinate Framework (CCF) currently serves as the standard atlas
resource with which to map and integrate results from different studies. The neuroscience community, on the
other hand, does not have similar CCFs for the developing mouse brain. The lack of developmental CCFs
significantly hinders progress on cell type mapping of the developing mouse brain by limiting the reproducibility
and integration of data from different studies. To address this deficiency, we have assembled a highly synergistic,
multi-institutional team with complementary skill sets to create developmental CCFs with associated ontology
and true 3D anatomical labels while also demonstrating the application of our CCFs by generating quantitative
mappings of GABAergic neurons in the developing mouse brain. Toward this end, we will first utilize MRI and
light sheet fluorescent microscopy (LSFM) to develop high-resolution developmental CCFs at seven different
developmental time points (E11.5, E13.5, E15.5, E18.5, P4, P14, and P56) with different cellular features,
including total cell density, myelination, and neurovasculature. Second, we will create true 3D anatomical labels
for the CCFs based on cellular and gene expression information, and build a comprehensive ontology that will
allow anatomical region changes to be linked across development and maturation. Lastly, we will generate a
cellular-resolution quantitative map of GABAergic neuronal subtypes using tissue clearing and LSFM imaging in
developing mouse brains, which will serve as a substantial data resource to accelerate developmental
neuroscience discovery. The successful completion of this project will enable a broad field of scientists to
leverage modern brain mapping technologies more effectively in studying the developing mouse brain.

## Key facts

- **NIH application ID:** 10088508
- **Project number:** 1RF1MH124605-01
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** JAMES C GEE
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $3,797,901
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10088508

## Citation

> US National Institutes of Health, RePORTER application 10088508, Establishing Common Coordinate Framework for Quantitative Cell Census in Developing Mouse Brains (1RF1MH124605-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10088508. Licensed CC0.

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