# Human cerebral organoids as a model system for neural development and disease

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $249,000

## Abstract

Project Summary/Abstract
It is intriguing how a single fertilized egg divides and gives rise to an organism containing a diverse array of
cells, tissues, and organs with beautiful three-dimensional (3D) architecture in a precise manner. The
neocortex is of particular interest because it is highly-specialized structure with features that are markedly
different between species. For example, the neocortex in primates is enormously increased in size and
complexity, which probably endow humans with remarkable sensory activities and intellectual ability such as
abstract thinking and creativity. Understanding human corticogenesis is important for not only to gain some
evolutionary insights but also to discover the underlying causes of human-specific diseases such as
neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. We ideally need a human brain
model, given that rodent models sometimes fail to mimic human symptoms and predict clinical outcomes.
However, due to limited access to human brain tissue and ethical concerns, it has been challenging to directly
study human development. Consequently, considerable attention has been placed on the generation of in vitro
models using human pluripotent stem cells (hPSCs) to recapitulate aspects of human development and
disease. The cerebral organoid is a 3D cortical tissue derived from hPSCs and recapitulates laminar
organization of the developing cerebral neocortex in vivo. The advent of such organoid techniques has opened
the door for studies of human specific developmental features and paves the way for disease modeling.
However, many organoid differentiation protocols are inefficient and inconsistent and display marked variability
in their ability to recapitulate the 3D architecture and course of neurogenesis in the developing human brain.
The goal of this proposal is to understand 1) the state of hPSCs that can predict efficient and successful
organoid differentiation, 2) to use this robust organoid system to uncover microcircuit formation that has the
underlying importance for human brain activities and its malfunction is likely link to neuropsychiatric disorders,
such as autism, and 3) to study Fragile X Syndrome, the most common heritable form of cognitive impairment,
using human cortical organoids that can give some human-specific insights into mechanisms and cures of this
disease.

## Key facts

- **NIH application ID:** 10208031
- **Project number:** 4R00HD096105-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Momoko Watanabe
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208031

## Citation

> US National Institutes of Health, RePORTER application 10208031, Human cerebral organoids as a model system for neural development and disease (4R00HD096105-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10208031. Licensed CC0.

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