# GENETIC CONTROL OF NEMATODE VULVAL DEVELOPMENT

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 1994 · $111,048

## Abstract

The goal of this project is to understand the molecular basis for how
intercellular signals control cell-type determination during animal
development.  During vulval induction in the nematode Caenorhabditis
elegans, a single gonadal cell induces three of six multipotent epithelial
precursor cells to proliferate and generate differentiated vulval cells.
Genetic analyses have defined genes necessary for this inductive process.
Three such genes encode nematode homologs of mammalian proto-oncogenes
involved in signalling, and act in a common pathway.  The predicted lin-3
gene product, which contains a single epidermal growth factor [EGF] repeat,
is a candidate for the inductive signal.  the let-23 gene product, a
transmembrane tyrosine kinase of the EGF-receptor family, is a candidate
for the receptor for the inductive signal.  the let-60 gene product, a ras
protein, acts as a switch that controls cell type in response to lin-3 and
let-23.  This study will use classical genetics, molecular cloning,
transgenic nematodes, and biochemical methods to understand the function of
these proto-oncogenes in intercellular signalling, and to identify novel
components of this signalling pathway.  The specific aims of this proposal
are to test the hypotheses that lin-3 encodes the inductive signal and let-
23 encodes its receptor; to characterize the negative regulation of the let
-23 receptor by studying genes, as well as domains of let-23, that modulate
the activity of this receptor; to identify genes that couple the let-23
tyrosine kinase and let-60 ras, and to identify genes that act after the
let-60 ras protein to activate vulval differentiation.  Nematode vulval
induction provides an excellent opportunity to study, in the context of a
developing animal, the action of gene products whose mutant forms result in
cell transformation and cancer.  The strong conservation of these gene
products and this signal transduction pathway throughout evolution makes it
likely that novel gene products identified by these studies of vulval
induction will help elucidate how intercellular signalling works during
mammalian development.

## Key facts

- **NIH application ID:** 2198921
- **Project number:** 5R01HD023690-07
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **SAM.gov UEI:** U2JMKHNS5TG4
- **Principal Investigator:** PAUL Warren STERNBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $111,048
- **Award type:** 5
- **Project period:** 1988-02-01 → 1996-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198921

## Citation

> US National Institutes of Health, RePORTER application 2198921, GENETIC CONTROL OF NEMATODE VULVAL DEVELOPMENT (5R01HD023690-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198921. Licensed CC0.

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