# Gene-ethanol interactions underlying aberrant neuronal cell behaviors

> **NIH NIH F32** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $71,430

## Abstract

Project Summary
Fetal Alcohol Spectrum Disorders (FASD) is an umbrella term used to describe a myriad of defects associated
with prenatal alcohol exposure, including damage to the central nervous system. Alcohol is the most common
teratogen, and is recognized as the leading preventable cause of birth defects and developmental disabilities.
FASDs are estimated to affect as high as 2 to 5% of children in the United States. While fetal alcohol exposure
is widely known to cause FASDs, we understand very little about gene-ethanol interactions and how these
interactions elicit abnormal cell behaviors. The behaviors of cells contribute to brain morphogenesis and
function. A fundamental cell behavior in the developing brain is neuronal migration. Motor neurons in the
vertebrate hindbrain migrate dynamically. These dynamic behaviors are orchestrated by complex genetic
hierarchies. Members of the Wnt/planar cell polarity (PCP) signaling pathway, such as vangl2, are highly
involved in determining these migratory behaviors. Facial branchiomotor neurons (FBMNs) are a subset of
hindbrain neurons that migrate extensively via tangential and radial migratory mechanisms. My preliminary
data demonstrate that ethanol interacts with vangl2 during tangential and radial FBMN migration. FBMN
migration fails to occur in both control and ethanol-exposed vangl2 mutants. While control vangl2
heterozygotes develop normally, ethanol induces a variety of FBMN defects. Strikingly, many ethanol-exposed
vangl2 heterozygotes completely phenocopy the mutant. I hypothesize that combined genetic and ethanol-
mediated attenuation of planar cell polarity results in the mispositioning of cranial motor neurons. In Specific
Aim 1 of this proposal, I will use live time-lapsed confocal analyses to assess the tangential and radial
migratory behaviors of FBMNs using a transgene to label hindbrain motor neurons. In Specific Aim 2, I will
characterize vangl2-ethanol interactions underlying neuronal migration defects. I will use in situ
marker analyses to analyze hindbrain patterning and readouts of planar cell polarity to determine the
interaction of ethanol with the Wnt/PCP pathway. In Specific Aim 3, I will map and functionally characterize
ethanol-sensitive mutants that are identified through our ongoing forwards genetic screen. This proposal will
provide insight to mechanisms of gene-ethanol interactions that lead to the variety of neural defects associated
with FASD. In addition, the data generated from this proposal will be directly applicable to humans due to the
high conservation of gene function across vertebrates. This will allow for better identification of individuals at
most risk and help with the development of FASD therapeutic treatments.

## Key facts

- **NIH application ID:** 9962208
- **Project number:** 5F32AA026770-03
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Desire Buckley
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $71,430
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962208

## Citation

> US National Institutes of Health, RePORTER application 9962208, Gene-ethanol interactions underlying aberrant neuronal cell behaviors (5F32AA026770-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9962208. Licensed CC0.

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