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Related Concept Videos

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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...

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Related Experiment Video

Updated: Jul 16, 2026

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
07:26

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

Published on: January 31, 2025

Multiple ubiquitin-dependent processing pathways regulate hedgehog/gli signaling: implications for cell development

Lucia Di Marcotullio1, Elisabetta Ferretti, Azzura Greco

  • 1Department of Experimental Medicine and Pathology, Cenci Bolognetti Foundation, University La Sapienza, Roma, Italy.

Cell Cycle (Georgetown, Tex.)
|February 22, 2007
PubMed
Summary

Numb and Itch E3 ligase form a regulatory loop that limits Hedgehog signaling in neural stem cells. This pathway

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Cell Population Analyses During Skin Carcinogenesis
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Cell Population Analyses During Skin Carcinogenesis

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Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
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Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells

Published on: September 1, 2010

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Last Updated: Jul 16, 2026

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

Published on: January 31, 2025

Cell Population Analyses During Skin Carcinogenesis
06:53

Cell Population Analyses During Skin Carcinogenesis

Published on: August 21, 2013

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

Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells

Published on: September 1, 2010

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Neuroscience
  • Oncology

Background:

  • The Hedgehog signaling pathway is essential for neural stem cell maintenance and tumorigenesis.
  • E3 ubiquitin ligases regulate Gli transcription factors, controlling Hedgehog pathway activity.
  • Previous studies identified Cullin-based ligases; the HECT family ligase Itch is a new player.

Purpose of the Study:

  • To investigate the role of the HECT family E3 ligase Itch in regulating Hedgehog signaling.
  • To identify novel regulators of Gli1 degradation and their impact on neural development and brain tumors.
  • To elucidate the function of Numb in the context of Hedgehog signaling and medulloblastoma.

Main Methods:

  • Identification of Itch as an E3 ligase targeting Gli1 for ubiquitination and degradation.
  • Characterization of Numb's role in promoting Itch-dependent Gli1 ubiquitination.
  • Analysis of Numb expression and function in cerebellar progenitors and medulloblastoma cells.

Main Results:

  • Itch directly ubiquitylates and degrades Gli1, a key downstream effector of Hedgehog signaling.
  • Numb promotes Itch-mediated Gli1 degradation, suppressing Gli1's transcriptional activity.
  • Numb downregulation in cerebellar progenitors correlates with medulloblastoma and loss of its anti-proliferative effects.

Conclusions:

  • A novel Numb/Itch-dependent regulatory loop limits Hedgehog signaling during neural progenitor differentiation.
  • This regulatory loop suppresses Gli1 activity, exerting anti-proliferative and pro-differentiation effects.
  • Subversion of the Numb/Itch pathway is implicated in brain tumorigenesis, particularly medulloblastoma.