# Molecular mechanisms in development

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $965,416

## Abstract

Project Summary/Abstract
The goal of this program is to understand how informational signaling proteins that pattern tissues distribute in
space and time during development. We study this process in Drosophila, investigating the Decapentaplegic,
Hedgehog, FGF, EGF, Wg, and Notch-Delta signaling systems. The mechanisms that move these proteins
from their sources and distribute them to their targets involve cellular machines and organelles whose actions
precisely control their movement, and our work has identified novel structures we named “cytonemes” that
mediate their dispersion. This proposal describes the approaches we will take to further characterize
cytonemes and the machines and organelles that make them work.
Cytonemes are specialized filopodia that extend between cells that produce signaling proteins and their
signaling targets. Our work has now established that cytonemes are key elements of paracrine cell-cell
signaling, and their properties led us to propose that signaling proteins move between non-neuronal cells in a
manner similar to the way neurons exchange signals with post-synaptic target cells – by exchanging
information at synaptic contacts that connect cell extensions such as axons that span the distance between
signaling and target cells. Findings made during the current grant period show that both the composition and
activities of cytonemes are remarkably similar to axons and chemical synapses. Cytonemes are constituted
with proteins that have been shown to function and to be required at neuronal synapses, such as the cell
adhesion proteins Capricious and Neuroglian, and are calcium dependent, excitable, and glutamatergic. They
require the glutamate receptor, glutamate transporter, voltage-gated calcium channel, synaptobrevin, and
synaptotagmin. We have also learned that cytonemes have alternating regions of thin and wide diameter akin
to “beads on a string”, and borrow deep into invaginations of target cells. These unexpected properties have
fascinating implications for mechanisms of pathfinding and signal transduction, and the work we propose both
develops new tools for imaging cytonemes and builds upon our previous findings to determine the roles,
composition and functions of these remarkable organelles and this mechanism of contact-based signaling.

## Key facts

- **NIH application ID:** 10813085
- **Project number:** 5R35GM122548-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** THOMAS B. KORNBERG
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $965,416
- **Award type:** 5
- **Project period:** 2017-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813085

## Citation

> US National Institutes of Health, RePORTER application 10813085, Molecular mechanisms in development (5R35GM122548-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10813085. Licensed CC0.

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