# Regulation of Development by LRP4 at Drosophila Peripheral Synapses

> **NIH NIH F31** · THOMAS JEFFERSON UNIVERSITY · 2020 · $45,520

## Abstract

Project Summary
The nervous system is a vastly complex network which develops through intricate and tightly regulated
processes. One critical aspect of neurodevelopment is the formation of connections between neurons. Synapses
form through a series of complex steps to ensure their lasting functionality throughout the life of an organism.
The regulation of these steps is essential for proper synaptic organization, but the molecular mechanisms that
underlie these events remain incompletely understood. Knowledge of these processes is central to the
understanding of cellular events that occur during synaptic development, as well as the mechanisms which may
be impaired in neurodevelopmental disorders, including autism. The goal of this F31 Ruth L. Kirchstein NRSA is
to address fundamental questions about synaptic development.
This proposal aims to elucidate a novel mechanism of synaptic development by investigating the cell surface
receptor LRP4. This protein has a well-defined role at the developing mammalian neuromuscular junction (NMJ),
but has recently been found at other synapses, with more enigmatic functions. At the mammalian NMJ, LRP4
functions postsynaptically in conjunction with Agrin and MuSK. At other synapses, including in the Drosophila
CNS, LRP4 has been found presynaptically and independent of Agrin and MuSK. Preliminary data at the
Drosophila larval NMJ also indicates an important role in synaptic development. This synapse provides an
opportunity for dissection of a novel mechanism by which LRP4 functions during synaptic development, given
the availability of molecular genetics tools and achievability of single synapse resolution.
The cellular events governed by LRP4 at the Drosophila NMJ will be assessed using high resolution imaging,
genetics, and biochemistry. Expression studies will inform whether LRP4 functions at the presynapse or
postsynapse to promote development. Analysis of loss of function phenotypes will determine the developmental
processes regulated by these genes of interest. Genetic and biochemical approaches will eludicate the pathway
by which these processes are regulated. Overall, these studies will provide unique insights into a novel role for
LRP4 in regulating synaptic development. This project will inform the understanding of fundamental
developmental mechanisms, and provide insights into neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 10157224
- **Project number:** 1F31NS120718-01
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Alison DePew
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157224

## Citation

> US National Institutes of Health, RePORTER application 10157224, Regulation of Development by LRP4 at Drosophila Peripheral Synapses (1F31NS120718-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10157224. Licensed CC0.

---

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