# Mechanisms for cell-cell interactions to intiate dendrite outgrowth

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2020 · $328,125

## Abstract

The axons, dendrites, and synapses of individual neurons must be positioned at appropriate targets to establish
and maintain functional neural circuits. Our long-term goals are to elucidate how cellular signaling
establishes neural circuits, to understand how cellular communication translates into neural
morphogenesis, and to dissect how disruption of neural circuit assembly may result in impairments in
neurodevelopmental disease. A core principle in brain development is that circuit assembly and neural
morphogenesis require spatiotemporal regulation of cytoskeletal remodeling mediated by both intracellular and
extracellular signaling. However, while the signaling pathways that guide axonal outgrowth have been
extensively characterized, the pathways that direct dendrites into their target fields remain obscure, in large part
due to the complicated morphology and small size of dendritic branches. Using the Drosophila aCC motoneuron,
which has a highly stereotyped, simple dendrite pattern, and molecular marker systems that allow examination
of individual cells in complex environments, we have recently gained insight into the specification of
dendritogenesis by inter-neuronal interactions. 1) We found that interaction between the aCC and its target
neuron (MP1) is mediated by Down syndrome cell adhesion molecule (Dscam1). 2) The Dscam1 receptor
recruits the Dreadlocks (Dock) adapter protein and the Pak1 kinase to the membrane in the aCC. 3)
Subsequently, Pak1 interacts with activated Cdc42 GTPase, leading to cytoskeletal rearrangements at the
contact site. These findings have led to a novel model in which the Dscam1-Dock-Pak1 and the Cdc42 pathways
converge to regulate aCC dendritogenesis. Using a combination of genetics, biochemistry and microscopy
techniques, the objective of this project is to address key gaps in our understanding of dendrite specification by
this signaling pathway. In Aim 1, to define the potential role of the secreted ligand Slit in mediating Dscam1
interactions at the aCC-MP1 contact site, we will examine whether a glycoprotein called Slit facilitates
communication between Dscam1 receptors on the aCC and the MP1 neurons. In Aim 2, to elucidate the
mechanism by which Dscam1 interactions lead to Y-phosphorylation in the cytoplasmic domain, we will
investigate how ligand binding promotes tyrosine phosphorylation of Dscam1 to stimulate Dock binding. In Aim
3, to identify upstream signaling that activates Cdc42 and aCC dendritogenesis, we will examine whether the
Ephrin receptor activates Cdc42 at the onset of aCC dendritogenesis via an Eph-interacting guanine nucleotide
exchange factor (Ephexin). The proposed studies will provide significant insights into the molecular mechanism
of dendritogenesis in the CNS, a critical process that is greatly under-explored. In the long term, these studies
will provide a foundation for understanding the etiology and potential treatment of neurodevelopmental diseases.

## Key facts

- **NIH application ID:** 9970547
- **Project number:** 5R01NS107558-03
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Daichi Kamiyama
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $328,125
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970547

## Citation

> US National Institutes of Health, RePORTER application 9970547, Mechanisms for cell-cell interactions to intiate dendrite outgrowth (5R01NS107558-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9970547. Licensed CC0.

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