# DIP-ÃÂÃÂ± is required for synaptic elaboration and function

> **NIH NIH F31** · UNIVERSITY OF CHICAGO · 2022 · $35,772

## Abstract

Project Summary/ Abstract
The overall goal of this project is to identify the molecular determinants that act in the neuron and/or its target
to promote the context-specific synaptic arbor elaboration and maintenance required for proper function. Once
neurons find their synaptic partners, synaptic terminals must expand to an appropriate size to maintain
synaptic fidelity. While the guidance cues that direct axons to their target area are well characterized, less is
known about the molecular mechanisms that produce the stereotyped growth patterns unique to each synaptic
terminal arbor. The clear link between dysfunction in circuit maintenance/synaptic transmission and
neurological disease, such as autism and schizophrenia, underscores the urgency in delineating these
molecular pathways. The strategy proposed to investigate this important developmental process is to examine
how the Dpr and DIP subfamilies of Ig-domain cell-surface proteins (CSPs), instruct synaptic terminal
elaboration and function. I will leverage the relative simplicity of the Drosophila neuromuscular circuit and the
powerful genetic tools available to examine these questions with single-synapse resolution. My central
hypothesis is that these CSPs initially determine target-specific synaptic arbor elaboration, and concurrently,
organize synaptic active zones. To test this hypothesis, I will focus on DIP-α since my preliminary data
suggests novel roles for DIP-α in both processes. In Aim 1, I will utilize cell-specific reporters to examine all
motor neurons that express DIP-α to determine DIP-α’s role is in instructing elaboration of specific synaptic
terminal arbors. I will employ a candidate based genetic screen in order to uncover potential mechanisms. In
Aim 2, I will characterize DIP-α’s role in forming new and/or sculpting existing active zones through localization
of a core active zone scaffolding protein. Additionally, I will perform simultaneous electrophysiological
recordings and optogenetics to analyze motor neuron specific responses. From these studies, I anticipate
unraveling new roles for DIPs in synapse specific elaboration and synaptogenesis. This proposal is innovative
in that it combines interdisciplinary approaches, including electrophysiology, biochemistry, single-cell genetic
manipulations, and microscopy, to elucidate fundamental mechanisms governing synaptic arbor expansion and
neurotransmission. This research is significant because it addresses a long-held question in developmental
neurobiology: how do discrete synaptic arbors of the same neuron acquire unique morphologies. Lastly, this
project provides an ideal training opportunity to support my long-term professional goal of becoming an
independent investigator focused on elucidating novel molecular mechanisms that underlie neural circuit
development, and importantly, contributes to our understanding of how these molecular pathways can be
disrupted to reveal disease etiologies.

## Key facts

- **NIH application ID:** 10477294
- **Project number:** 5F31NS120458-03
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Meike Lobb-Rabe
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $35,772
- **Award type:** 5
- **Project period:** 2020-09-30 → 2023-04-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477294

## Citation

> US National Institutes of Health, RePORTER application 10477294, DIP-ÃÂÃÂ± is required for synaptic elaboration and function (5F31NS120458-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10477294. Licensed CC0.

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