# A new molecular code for the development of synapse specificity

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $366,084

## Abstract

PROJECT SUMMARY/ABSTRACT
The ability of neurons to selectively synapse with correct cell types amidst many alternatives (here referred to
as synaptic specificity) underlies the structure and function of the nervous system. With respect to progress
made in illuminating mechanisms governing the guidance and patterning of axons and dendrites, our
knowledge of how synaptic specificity is achieved is severely limited. Addressing this gap in knowledge is
essential to understanding how the precision of neural connectivity is established. Our goal is to identify
general molecular strategies underlying synaptic specificity. Progress in this area has been limited by the
difficulty in studying synapse formation with precise molecular and cellular resolution in complex regions.
Therefore, we focus on the Drosophila visual system, wherein cell types and synapses between them are well-
characterized, and it is feasible to interrogate gene function in a cell autonomous manner. It is widely believed
that neurons identify correct synaptic partners through use of complementary cell surface tags that function like
a “lock and key”. However, evidence supporting this idea is scarce. Previously, we found that members of two
subfamilies of the immunoglobulin superfamily (IgSF), dprs (21 members) and dpr-interacting proteins (DIPs)
(9 members) which bind heterophilically, are expressed in a matching manner between synaptic partners in the
Drosophila visual system. Based on our preliminary findings, we hypothesize that dpr-DIP interactions regulate
synaptic specificity by biasing synapse formation towards specific cell types, thereby preventing promiscuous
synapse formation with incorrect partners. In this model, dpr-DIP interactions are not necessary for
synaptogenesis, but promote synapse formation between specific cell types, potentially by controlling the
location of synaptic machinery. We will test this hypothesis in 3 Specific AIMs. In AIMs I and II, we perform
focused studies at specific synapses in the lamina to determine if dpr-DIP interactions (I) are necessary to
prevent synapse formation with incorrect partners, and (II) have the capacity to promote synapse formation
between specific cell types. In AIM III, we will test whether dpr-DIP interactions generally control synaptic
connectivity in the visual system through broader studies in a different region of the optic lobe (medulla), which
address (1) the function of diverse dpr-DIP interactions at multiple synapses, and (2) whether complementary
dpr/DIP expression is generally predictive of synaptic connectivity. In general, our data support the
longstanding idea that neurons identify correct synaptic partners through complementary cell surface tags that
function like a “lock and key”. However, we propose that such molecules are not necessary for
synaptogenesis, and rather control synaptic specificity by limiting promiscuous synapse formation. This
research will advance fundamental knowledge of how neurons sel...

## Key facts

- **NIH application ID:** 9858439
- **Project number:** 5R01NS110713-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** David D GINTY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $366,084
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858439

## Citation

> US National Institutes of Health, RePORTER application 9858439, A new molecular code for the development of synapse specificity (5R01NS110713-02). Retrieved via AI Analytics 2026-08-24 from https://api.ai-analytics.org/grant/nih/9858439. Licensed CC0.

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