# Quantifying the developmental trajectory of autism-associated brain overgrowth using 3D cellular resolution imaging

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $425,816

## Abstract

Project Summary/Abstract
Brain development involves the organized differentiation of neural progenitors into neurons and glia, tightly
orchestrated in both temporal and spatial domains. Alterations in embryonic brain development can manifest
as altered post-natal brain structure and function, leading to neuropsychiatric illness. Recent advances in
tissue clearing technology and light-sheet microscopy have allowed for rapid cellular resolution image
acquisition in intact whole brains. The ability to analyze these large datasets has lagged behind the ability to
acquire them, resulting in their most common use as visual anecdotes rather than quantified results. In this
proposal, we will develop computational tools to specifically quantify the developmental trajectories of
individual cell-types in the entire brain. We will apply tissue clearing technology and light-sheet microscopy to
study how development is altered in autism-associated CHD8 heterozygous mutant mice. Heterozygous CHD8
loss of function mutations result in macrocephaly in both human patients and mouse models. We will first
acquire whole brain cellular resolution images of neural progenitor and neuronal cell-types across critical time-
periods of neocortical neurogenesis in wild-type and Chd8+/- mice. We will then develop longitudinal image
registration algorithms to map the developmental trajectories of neocortical development. Finally, we will
quantify cell-type distributions within annotated areas of the developing neocortex. Completing the aims of this
proposal will elucidate the cellular basis and spatial localization of brain overgrowth in autism.

## Key facts

- **NIH application ID:** 10434849
- **Project number:** 5R01MH121433-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jason Louis Stein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $425,816
- **Award type:** 5
- **Project period:** 2019-09-23 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434849

## Citation

> US National Institutes of Health, RePORTER application 10434849, Quantifying the developmental trajectory of autism-associated brain overgrowth using 3D cellular resolution imaging (5R01MH121433-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10434849. Licensed CC0.

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