Related Experiment Video

Updated: Jun 17, 2026

Live-cell Imaging of Sensory Organ Precursor Cells in Intact Drosophila Pupae
04:27

Live-cell Imaging of Sensory Organ Precursor Cells in Intact Drosophila Pupae

Published on: May 27, 2011

The evolutionarily conserved TSC/Rheb pathway activates Notch in tuberous sclerosis complex and Drosophila external

Magdalena Karbowniczek1, Diana Zitserman, Damir Khabibullin

  • 1Institute for Cancer Research, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA

The Journal of Clinical Investigation
|December 30, 2009
PubMed

Insights

Tuberous sclerosis complex (TSC) gene mutations disrupt cell fate by altering Notch signaling. This study reveals TSC and Rheb regulate cell division and Notch activity, potentially explaining TSC

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • Mutations in TSC1 and TSC2 genes cause tuberous sclerosis complex (TSC), a disorder with unusual tumor cell lineage patterns.
  • The mechanisms behind these aberrant cell-fate determination patterns in TSC remain poorly understood.

Purpose of the Study:

  • To investigate the role of the TSC in regulating cell-fate decisions during asymmetric cell division in the Drosophila external sensory organ (ESO).
  • To explore the connection between TSC, Rheb, and Notch signaling in both Drosophila and human TSC-associated tumors.

Main Methods:

  • Utilized Drosophila ESO as a model system to study asymmetric cell division.
  • Performed live imaging to observe cell-fate switching during ESO development.
  • Analyzed human angiomyolipomas and TSC2-mutant cell lines for Notch pathway activation.
  • Used gamma-secretase inhibitors to assess the impact of Notch inhibition on cell proliferation in a xenograft model.

Main Results:

  • Inactivation of Tsc1 or Rheb overexpression in Drosophila ESO led to duplication of pIIa cell progeny (bristle, socket) and loss of pIIb cell progeny (neuron).
  • This cell-fate switch was observed at the pIIa-pIIb 2-cell stage.
  • Evidence of Notch receptor cleavage and target gene activation was found in human angiomyolipomas.
  • TSC2-deficient cells showed Rheb-dependent Notch activation, and Notch inhibition suppressed Tsc2-null cell proliferation.

Conclusions:

  • The TSC and Rheb proteins regulate Notch-dependent cell-fate decisions in Drosophila.
  • Dysregulation of Notch signaling by TSC and Rheb occurs in mammalian cells.
  • Aberrant Notch activity may contribute to the characteristic features of tuberous sclerosis complex.

More Related Videos

Visualizing Low-Abundance Proteins and Post-Translational Modifications in Living Drosophila Embryos via Fluorescent Antibody Injection07:15

Visualizing Low-Abundance Proteins and Post-Translational Modifications in Living Drosophila Embryos via Fluorescent Antibody Injection

Published on: January 19, 2024

Visualization of Proprioceptors in Drosophila Larvae and Pupae09:51

Visualization of Proprioceptors in Drosophila Larvae and Pupae

Published on: June 13, 2012

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...