# Genetic Analyses of Dendrite Development in Caenorhabditis elegans

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $365,313

## Abstract

PI: Buelow, Hannes E.
 Project Summary
 Behavior in multicellular organisms is controlled by neural circuits, which consist of interconnected
neurons that integrate synaptic input, and compute output. Most neurons are bipolar and comprise
dendrites and axons, which mediate reception and transmission of information, respectively. Dendrite
branching is necessary for correct circuit assembly. While great strides have been made to
understand axon development and branching, less is known about dendrite development. We are
using the pair of PVD and FLP neurons in the small nematode C. elegans to investigate basic genetic
and molecular mechanisms of dendrite development. Both PVD and FLP neurons elaborate highly
branched dendritic arbors that employ conserved mechanisms during dendrite development. In a
genetic screen for loci required for the formation of the stereotypic dendritic arbors of PVD neurons,
we retrieved mutants with defects in PVD dendrite morphogenesis. Analyses of several of these
genes identified the `menorin' pathway. This pathway is comprised of the conserved novel cell
adhesion molecule MNR-1/menorin that acts in a complex with the adhesion molecule SAX-7/L1CAM
from the skin through a leucine rich transmembrane receptor on PVD dendrites. In addition, we have
found that the proprotein convertase kpc-1/furin acts genetically in the menorin pathway and that
catalytic activity is required in PVD for patterning different aspects of dendritic arbor development.
This proposal is aimed at two basic questions that arise from our published and unpublished studies.
First, what are the in vivo targets of the proprotein convertase KPC-1/furin during these processes?
Second, what may be the signaling pathway(s) operating within the PVD (or FLP) neurons? In the
first aim we will define and characterize in vivo targets of the proprotein convertase kpc-1/furin that
we have identified by a combination of proteomics and a candidate gene approach. In a second aim
we will analyze the function of a novel extracellular protein, which has not previously been implicated
in PVD dendrite development and which also appears to act in the `menorin' pathway. In a third aim,
we will conduct a phenotypic, genetic and molecular characterization of an intracellular signaling
molecule, which acts in PVD within the menorin pathway and likely downstream of the DMA-1
transmembrane receptor. In sum, our studies are aimed at a better understanding of basic aspects of
dendrite development by focusing on non-autonomous mechanisms that in conjunction with a novel
pathway pattern development of somatosensory dendrites.

## Key facts

- **NIH application ID:** 9942532
- **Project number:** 5R01NS096672-06
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Hannes Erich Buelow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $365,313
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942532

## Citation

> US National Institutes of Health, RePORTER application 9942532, Genetic Analyses of Dendrite Development in Caenorhabditis elegans (5R01NS096672-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9942532. Licensed CC0.

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