Related Experiment Video

Updated: Jun 13, 2026

Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
06:32

Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells

Published on: September 1, 2010

Notch signaling is not essential in sonic hedgehog-activated medulloblastoma

B A Hatton1, E H Villavicencio, J Pritchard

  • 1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Oncogene
|May 5, 2010
PubMed

Insights

Notch signaling is not essential for sonic hedgehog (shh)-activated medulloblastoma initiation or growth. Gamma secretase inhibitors did not impact tumor progression in mouse models, challenging previous findings.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Dysregulated Notch signaling is implicated in human and mouse medulloblastoma.
  • Gamma secretase inhibitors (GSIs) block Notch signaling by inhibiting protein cleavage.
  • Prior in vitro studies suggested GSIs impair medulloblastoma cell engraftment.

Purpose of the Study:

  • To quantify Notch signaling's contribution to sonic hedgehog (shh)-activated mouse medulloblastoma.
  • To investigate the role of Notch pathway in medulloblastoma initiation, engraftment, and maintenance.

Main Methods:

  • Utilized in vivo genetic and pharmacologic approaches in mouse models.
  • Administered GSIs to pharmacologically inhibit Notch pathways.
  • Generated genetically engineered mouse medulloblastoma models with bi-allelic absence of Notch1, Notch2, or Hes5 genes.

Main Results:

  • Pharmacologic Notch inhibition did not reduce medulloblastoma xenotransplantation efficiency.
  • Systemic therapy did not impact tumor size, proliferation, or apoptosis in mouse models.
  • Absence of Notch1, Notch2, or Hes5 genes did not alter medulloblastoma incidence or pathology in SmoA1-driven models.

Conclusions:

  • Notch signaling is not essential for the initiation, engraftment, or maintenance of shh-driven medulloblastomas.
  • Findings contrast with previous in vitro studies, highlighting the importance of in vivo validation.

More Related Videos

Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis10:25

Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis

Published on: December 12, 2019

Stimulation of Notch Signaling in Mouse Osteoclast Precursors08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

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...
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...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...