# Specialized junctions in the development of epithelia and neural circuits

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $254,250

## Abstract

Summary
 Adhesion between cells is important for the development of both epithelial tissues and neural
circuits, and a growing number of adhesion molecules have been found to act in both contexts. For
example, Sidekicks (Sdks) are immunoglobulin family members that mediate adhesion between specific
synaptic partners in the vertebrate retina. Drosophila Sdk was recently shown to act as a hub for the
assembly of tricellular adherens junctions (tAJs), which control tension at points where three epithelial cells
meet, in addition to its function in the visual motion detection circuit. This proposal will investigate the
mechanisms of Sdk localization and function in both contexts and explore possible connections between
them. The first aim will investigate whether the localization of Sdk to tAJs is driven by the fit between its
three-dimensional structure and their geometry. Sdk has been shown to recruit Polychaetoid and Canoe,
which anchor the ends of actin filaments, to tAJs. However, Sdk can also interact with the WAVE regulatory
complex, which promotes actin branching. The hypothesis that this interaction underlies the effect of Sdk on
junction lengthening, while Polychaetoid and Canoe promote junction shortening, will be tested. A yeast
two-hybrid screen will be used to identify additional factors that are recruited to tAJs by Sdk. The second
aim will examine the synaptic localization of Sdk in the visual system. Expansion microscopy will be used to
determine whether Sdk localizes to specific subregions of synapses between the Tm9 and T5 neurons,
and/or to a specific location on T5 dendrites. The effect on Sdk localization of structural alterations in the
protein and of tension in T5 will be tested. Finally, the possibility that epithelial interaction partners of Sdk
also colocalize and function with it at synapses will be investigated. This exploratory proposal will provide
insight into the assembly and function of the newly discovered tAJs, and may reveal a parallel structure at
synapses. Identifying the common features of epithelial and synaptic junctions will contribute to our
understanding of developmental disorders that affect either or both tissue types.

## Key facts

- **NIH application ID:** 10221016
- **Project number:** 5R21HD102660-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jessica E Treisman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $254,250
- **Award type:** 5
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221016

## Citation

> US National Institutes of Health, RePORTER application 10221016, Specialized junctions in the development of epithelia and neural circuits (5R21HD102660-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10221016. Licensed CC0.

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