# Investigating the effect of alcohol exposure on human cortical development using a 3D in vitro model

> **NIH NIH F32** · CHILDREN'S RESEARCH INSTITUTE · 2020 · $71,946

## Abstract

Project summary
 Alcohol consumption during pregnancy causes various developmental defects, including cognitive
deficit. The impairment of the central nervous system in patients of fetal alcohol spectrum disorder (FASD) has
been characterized intensively by non-invasive imaging and behavioral evaluations. While Ex vivo studies and
animal models provide snapshots of the molecular responses elicited by alcohol, the model systems do not
fully mimic the long gestational development of human brain. This proposal aims to develop a 3D in vitro model
using induced pluripotent cells (iPSC)-derived cortical spheroids to study the effect of ethanol on cortical
development, specifically on the outer subventricular zone (oSVZ). oSVZ is considered as an evolutionary
adaptive changes of human corticogenesis to increase the diversity of progenitor population, neuronal
production, and brain size. We are proposing to generate human iPSC-derived cortical spheroids in defined,
differentiation-promoting culture medium that is optimized for test of alcohol and other chemicals that produce
reactive oxidative stress. The development of stratified structure in the spheroids that were generated by our
novel protocol mimics the early process of human corticogenesis, which includes the formation of oSVZ like
structure. We will first match the developmental timeline of iPSC-derived cortical spheroids by
immunohistochemistry and RNA sequencing to human fetal brain, to clearly define the window for in vitro
FASD studies (Aim 1). Then we will incubate the iPSC-derived cortical spheroids in ethanol-containing medium
for different periods of time to mimic the prenatal exposure. We will assess the effects of ethanol on cortical
development by monitoring cell death, morphological change, cellular proliferation and the progenitor cell
population with an emphasis on oSVZ (Aim 2). Lastly, leveraging CRISPR/Cas9 genome editing technique, we
will demonstrate the applicability of our novel cortical spheroid system for investigation of molecular
mechanisms underlying alcohol-mediated cell pathology during human brain development. We will select
RBM39 as a target gene that was screened in our laboratory and functions defined in mouse cortex.
This study will not only characterize a powerful in vitro platform for studying human cortical development under
stress exposure, but also provide crucial insight into the mechanisms of FASD on cortical development at
cellular and molecular levels.

## Key facts

- **NIH application ID:** 10051307
- **Project number:** 5F32AA028163-02
- **Recipient organization:** CHILDREN'S RESEARCH INSTITUTE
- **Principal Investigator:** Ray Yueh Ku
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $71,946
- **Award type:** 5
- **Project period:** 2019-09-12 → 2022-09-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051307

## Citation

> US National Institutes of Health, RePORTER application 10051307, Investigating the effect of alcohol exposure on human cortical development using a 3D in vitro model (5F32AA028163-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10051307. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*