Related Experiment Video

Updated: May 30, 2026

The Drosophila Imaginal Disc Tumor Model: Visualization and Quantification of Gene Expression and Tumor Invasiveness Using Genetic Mosaics
10:31

The Drosophila Imaginal Disc Tumor Model: Visualization and Quantification of Gene Expression and Tumor Invasiveness Using Genetic Mosaics

Published on: October 6, 2016

A gain-of-function germline mutation in Drosophila ras1 affects apoptosis and cell fate during development

Christopher Gafuik1, Hermann Steller

  • 1Howard Hughes Medical Institute, The Rockefeller University, New York, New York, United States of America.

Plos One
|August 23, 2011
PubMed

Insights

Researchers identified the first gain-of-function mutation in Drosophila ras1, a homolog of human RAS genes. This mutation causes developmental defects, mirroring human RASopathies like Noonan syndrome, and aids in discovering new interacting genes.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • The RAS/MAPK pathway is crucial for transmitting signals from cell surface receptors to the nucleus, regulating gene expression.
  • Dysregulation of RAS signaling is implicated in oncogenesis and developmental disorders.
  • Germline mutations in RAS genes contribute to human diseases such as Noonan syndrome.

Purpose of the Study:

  • To identify and characterize the first gain-of-function germline mutation in Drosophila ras1, the homolog of human RAS genes.
  • To investigate the functional consequences of this mutation on development.
  • To utilize the mutant to discover novel interacting genes involved in RAS signaling.

Main Methods:

  • Identification and characterization of a Drosophila ras1 gain-of-function mutation (ras1(R68Q)).
  • Biochemical analysis of the mutant Ras protein's GTPase activity and GAP sensitivity.
  • Phenotypic analysis of developmental defects in homozygous mutant flies.
  • Genetic screens to identify interacting genes that suppress lethality or developmental defects.

Main Results:

  • A single amino acid substitution (R68Q) in the switch II region of Drosophila Ras1 was identified as a gain-of-function mutation.
  • The ras1(R68Q) mutant exhibits reduced intrinsic GTPase activity but normal GAP sensitivity.
  • Homozygous mutant flies display developmental defects, including altered cell fate and ectopic cell survival in the nervous system, indicative of elevated Ras signaling.
  • Novel interacting genes that suppress cell death were identified using the ras1(R68Q) mutant.

Conclusions:

  • The Drosophila ras1(R68Q) mutation serves as a valuable model for studying RASopathies.
  • This study provides insights into the biochemical and developmental consequences of germline RAS mutations.
  • The identified interacting genes offer potential targets for understanding and treating RAS-related developmental disorders.

More Related Videos

In Vitro Cleavage Assays using Purified Recombinant Drosophila Caspases for Substrate Screening08:16

In Vitro Cleavage Assays using Purified Recombinant Drosophila Caspases for Substrate Screening

Published on: October 6, 2022

Detecting Anastasis In Vivo by CaspaseTracker Biosensor20:16

Detecting Anastasis In Vivo by CaspaseTracker Biosensor

Published on: February 1, 2018

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...