# Genetic analysis of nematode cell differentiation

> **NIH NIH R35** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2020 · $768,083

## Abstract

Project Summary
 We will continue our study of genes needed for neuronal differentiation and
function using the six touch receptor neurons (TRNs) of the nematode Caenorhabditis
elegans. Our previous research identified genes needed for the generation,
specification, maintenance and function of the TRNs. In the last few years we 1)
identified genes needed for the specification of neuronal subtypes; 2) discovered a new
activity of transcription factors, including Hox proteins (as “guarantors”) that maintains
transcription factor expression by the restricting its stochastic expression; 3) examined
the how the release of epigenetic inhibition affects the terminal differentiation of
subtypes of motor neurons; 4) discovered several behaviors that modulate TRN touch
sensitivity, including a previous unstudied type – long-term sensitization – and the
mechanisms underlying these modulations; 5) identified a role for integrins and other
focal adhesion proteins in neuronal mechanosensation; 6) discovered that the -tubulin
acetyltransferase MEC-17 specifies the unusual, 15-protofilament structure of TRN
microtubules; 7) discovered a new type of chaperone for the mechanosensory
transduction channel; 8) determined the stoichiometry (MEC-42MEC-10) of the
transduction channel; and 9) investigated the roles of the Wnt signaling pathway, Rac
GTPases, and GEFs in process outgrowth. The general goal of the research going
forward is to exploit these findings to understand how the differentiation of individual cell
types is controlled and how mechanical inputs are sensed and modified. We plan to
discover and characterize genes needed for TRN differentiation, specifically those
needed for the differences among TRNs and TRN process outgrowth and ensheathment
and to investigate touch sensitivity and its control by investigating newly identified lethal
genes needed for touch sensitivity by testing and characterizing TRN-expressed genes
for supersensitivity, and by studying the role of neuropeptides. The health relatedness
of our work comes from the discovery of new genes and new interactions among genes
that are similar in humans and other mammals.

## Key facts

- **NIH application ID:** 9902460
- **Project number:** 5R35GM122522-04
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** MARTIN CHALFIE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $768,083
- **Award type:** 5
- **Project period:** 2017-04-14 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902460

## Citation

> US National Institutes of Health, RePORTER application 9902460, Genetic analysis of nematode cell differentiation (5R35GM122522-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9902460. Licensed CC0.

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