# Structural and behavioral impact of ASD-associated variants of NRXN1 in Drosophila melanogaster.

> **NIH NIH F32** · BAYLOR COLLEGE OF MEDICINE · 2020 · $33,723

## Abstract

Sleep disorders are common in patients diagnosed with autism spectrum disorders (ASD), being present
in upward of 80% of ASD youths. The sleep disruptions frequently last into adulthood, but it has been
difficult to elucidate a common neurobiological cause of these sleep disruptions. Previous research into
this phenomenon has noted circadian rhythm defects, frequent nighttime waking, and an overall
reduction in nighttime sleep: symptoms similar to what is reported in animal knock-out models of
NRNX1, a synaptic plasticity gene implicated in ASD. NRXN1 is currently known to interact with post-
synaptic proteins to stabilize synapses and promote neurite outgrowth, potentially acting as a common
source for both sleep disruptions and for neurite overgrowth phenotypes observed in ASD. Therefore,
identifying morphological changes in wake-promoting neurons during a cycling 24-hour time period will
be a necessary precursor to identifying a common molecular pathway for both ASD and sleep disorders.
In Drosophila, PDF neurons are an important part of the wake-promoting circuit, and are necessary for
the generation of stable sleep patterns. Recently, it has been shown that PDF neurons undergo
extensive remodeling, demonstrating cyclical periods of pruning and regrowth, over a 24 hour time
period. While previous studies have demonstrated the presence of Nrx-1, the Drosophila homologue for
NRXN1, in wake-promoting PDF neurons, it remains to be seen if the loss of Nrx-1 significantly impacts
the remodeling cycle observed in healthy animals.
As part of the proposed research, I will develop a Drosophila model of ASD by expressing human NRXN1
in a Nrx-1 null background. Specifically, I will evaluate if the loss of Nrx-1 significantly alters the cyclical
remodeling of Drosophila PDF neurons, and whether this effect can be rescued by the expression of
human reference NRXN1 or ASD-associated variant. I will then determine if this effect is sufficient to
disrupt sleep bouts, variations in the circadian rhythm, or alterations in stereotyped social behavior. This
proposed work will yield a new model with which to evaluate the effects of genes that contribute to
synaptic plasticity and provide needed information about the neurobiology of both sleep and ASD.

## Key facts

- **NIH application ID:** 10261321
- **Project number:** 5F32NS110174-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Jonathan Andrews
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $33,723
- **Award type:** 5
- **Project period:** 2018-09-20 → 2022-03-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10261321

## Citation

> US National Institutes of Health, RePORTER application 10261321, Structural and behavioral impact of ASD-associated variants of NRXN1 in Drosophila melanogaster. (5F32NS110174-03). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10261321. Licensed CC0.

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