# Cellular and Molecular Mechanisms of Forebrain Axon Pathfinding Defects in FASD

> **NIH NIH R21** · URSINUS COLLEGE · 2020 · $155,593

## Abstract

PROJECT SUMMARY
Despite public awareness campaigns, Fetal Alcohol Spectrum Disorders (FASD) remain prevalent due to
alcohol consumption by women who are pregnant or of child-bearing age. It is well appreciated that sensory
and motor information processing is distorted in FASD, but alcohol effects on the thalamus, which likely
mediates these functions, have not been widely investigated. Prenatal alcohol exposure (1) disrupts axonal
connections between the thalamus and cortex which are required to appropriately receive and respond to
sensory cues in the environment, (2) damages the ventral telencephalon (vTel), a critical intermediate target
for proper development of these connections, and (3) alters guidance cues and signaling pathways that
underlie cell and axon migration. We hypothesize that moderate alcohol exposure disrupts the Slit/Robo
pathway, a family of guidance cues and receptors that can have both direct and indirect effects on forebrain
axon formation. In this proposal we will investigate corridor-cell mediated thalamocortical axon (TCA) guidance
into and within the vTel using a mouse model of FASD. Our experiments aim to (1) define the nature of TCA
and corridor cell guidance errors in FASD and (2) establish Slit and Robo as molecular targets of FASD
neuropathology in vivo. To analyze TCA guidance errors, we will use dye tracing and immunostaining to
visualize these axons along their trajectory. To evaluate corridor cells, we will count and determine the
distribution of these cells via immunostaining. To analyze alcohol-induced perturbations of Slit and Robo
expression in vivo, we will perform western blotting and RT-PCR for each isoform. We will also use in vitro
explant co-cultures to test Slit and Robo function. In the FASD brain, we expect TCAs to project inappropriately
to intermediate and final targets and the corridor to be malformed. We also predict that Slit/Robo expression
and function will be suppressed. Our findings will reveal the impact of moderate alcohol exposure on guidance
mechanisms that are required for proper nervous system wiring, an area that is currently understudied. This
work will also enhance understanding of cellular and molecular mechanisms that are likely to be involved in
sensorimotor processing defects observed in human FASD. The proposed experiments will largely be carried
out by undergraduates who will be mentored to provide them the guidance and expertise needed for success
in science careers and graduate work.

## Key facts

- **NIH application ID:** 10017119
- **Project number:** 5R21AA025740-02
- **Recipient organization:** URSINUS COLLEGE
- **Principal Investigator:** Carlita Favero
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,593
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017119

## Citation

> US National Institutes of Health, RePORTER application 10017119, Cellular and Molecular Mechanisms of Forebrain Axon Pathfinding Defects in FASD (5R21AA025740-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10017119. Licensed CC0.

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