# Mechanisms that differentiate dendrite development from axon development

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $381,696

## Abstract

How a neuron’s dendrites and axons develop into distinct morphology—which is fundamental to the assembly
of neural circuits—is poorly understood. Understanding the mechanisms that differentiate dendrite and axon
development, therefore, is a vital goal in developmental neuroscience. Several regulatory mechanisms that are
dedicated to either dendrite-specific or axon-specific growth in vivo have been identified by taking advantage
of a Drosophila system. In addition, a molecular pathway that suppresses dendritic growth but promotes axonal
growth within the same neuron (i.e., a bimodal mechanism) has been located upstream of these dedicated
mechanisms. The bimodal regulation provides a unique mechanism for generating morphological diversity in
neurons, and is relevant for the design of effective strategies to regenerate an injured or diseased nervous
system. The long-term goal of this research is to define how a neuron develops into distinct subcellular parts
and how defects in this process lead to human disease. The objective of the proposed studies is to uncover the
molecular and cellular mechanisms of bimodal controls of dendritic and axonal growth. Recent studies have
shown that the evolutionarily conserved dual leucine zipper kinase/Wallenda (DLK/Wnd) pathway is a bimodal
regulator of dendritic and axonal growth, and that this pathway regulates the expression levels of a transcription
factor (Knot) and a cell adhesion molecule (Dscam) to control dendritic and axonal growth, respectively.
Preliminary studies suggest a novel concept: Translational regulation through RNA-binding proteins is at the
core of bimodal control of dendritic and axonal growth. The following model, which integrates specific molecules
and regulations with their spatial locations for bimodal control, will be tested: The DLK/Wnd pathway regulates
two distinct RNA-binding proteins to control PABP-dependent initiation of Dscam translation in axon terminals
for axonal growth and Knot expression in the cell body for dendritic growth, respectively. This model will be
tested by identifying (a) the molecular mechanism by which the DLK/Wnd pathway regulates axon-terminal
development and dendritic branch development and (b) the subcellular locations at which the DLK/Wnd
pathway regulates downstream factors to instruct the differential growth of dendrites and axons. The proposed
research is innovative because it proposes a novel concept in the differential development of dendrites and
axons and employs several innovative techniques that are well suited for this line of research. This research is
significant because it is expected to offer key insights into the coordination between dendritic and axonal
development, identify a critical role translational control plays in the differential development of dendrites and
axons, discover novel mechanisms by which the DLK/Wnd pathway functions in neurons, and provide insights
into the pathogenesis of neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 10217979
- **Project number:** 5R01MH112669-05
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** BING YE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $381,696
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217979

## Citation

> US National Institutes of Health, RePORTER application 10217979, Mechanisms that differentiate dendrite development from axon development (5R01MH112669-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10217979. Licensed CC0.

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