# Dendrite morphogenesis, function and regeneration

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $768,725

## Abstract

Project Summary/Abstract
For proper assembly of neuronal circuitry, axons have to be guided toward the correct targets and dendrites
need to have the correct branching pattern and structural specialization. Despite considerable recent
progress, much less is known about molecular mechanisms that control dendrite development as compared
to those controlling axon guidance. About 15 years ago, our lab initiated a fruitful genetic dissection of
dendrite development using Drosophila dendritic arborization (da) neurons as a model system. Multiple
genetic screens and the ensuing analysis of dendrite mutants have yielded important insights about the
molecular basis of dendrite development in Drosophila, including how axons and dendrites are made
differently, how a neuron acquires its neuronal type specific morphology, how the dendrites of different
neurons are organized relative to one another, how the size of a dendritic arbor is controlled, and how the
pruning and remodeling of dendrites are regulated during development. Many of the molecular mechanisms
controlling dendrite development have turned out to be conserved between Drosophila and mammals. Given
that defects in dendrites are strongly associated with diseases such as Down syndrome and a subset of
autism spectrum disorder, elucidating molecular pathways that control dendritic morphogenesis is not only of
great interest in basic neuroscience but also important for the potential relevance to neurological disorders.
As we continue to investigate the mechanisms that control dendrite morphogenesis, the knowledge we
have gained provide a solid foundation for exploring some very interesting and understudied areas about
dendrites: (1) The function of dendrites and the relationship between form and function. Drosophila da
neurons are sensory neurons; all of them are mechano-sensitive. This has led us to venture into the study of
mechano-sensation, the least well understood among our senses. Very few molecules have been firmly
established as mechano-transduction channels. By using da neurons, we discovered that NompC is a bona
fide mechano-transduction channel that enables the fly to sense gentle touch. We have also provided strong
evidence that NompC is gated mechanically by a tethering mechanism that involves the Ankyrin repeats of
NompC functioning as a gating spring. We propose to continue the in depth study of how NompC transduces
force. Furthermore, because there are still many novel mechano-sensitive channels that remain to be
discovered, we will use the fly sensory neuron as a model system to identify and study them. (2) Dendrite
regeneration after injury. By using da neurons that are well suited for studying both axon regeneration and
dendrite regeneration, we have been able to identify novel regulators of axon regeneration. Compare to axon
regeneration, much less is known about dendrite regeneration (a recent PubMed search revealed over 1400
papers on axon regeneration but only 4 on dendrite rege...

## Key facts

- **NIH application ID:** 10749874
- **Project number:** 5R35NS097227-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** YUH NUNG JAN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $768,725
- **Award type:** 5
- **Project period:** 2016-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10749874

## Citation

> US National Institutes of Health, RePORTER application 10749874, Dendrite morphogenesis, function and regeneration (5R35NS097227-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10749874. Licensed CC0.

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