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Hedgehog Signaling Pathway

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 Pathway

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...

Nociception

Nociception

Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain. Thus, pain helps the...

Notch Signaling Pathway

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 Renewal

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...

GPCR Desensitization

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...

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Related Experiment Video

Updated: May 29, 2026

An Improved Assay and Tools for Measuring Mechanical Nociception in Drosophila Larvae

An Improved Assay and Tools for Measuring Mechanical Nociception in Drosophila Larvae

Published on: October 29, 2020

Hedgehog signaling regulates nociceptive sensitization.

Daniel T Babcock¹, Shanping Shi, Juyeon Jo

¹Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Current Biology : CB

|September 13, 2011

Summary

Hedgehog (Hh) signaling is crucial for pain sensitization after tissue damage in fruit flies. Inhibiting Hh signaling in rats also impacts pain relief from morphine, suggesting Hh as a new pain treatment target.

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An Improved Assay and Tools for Measuring Mechanical Nociception in Drosophila Larvae

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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Published on: July 16, 2014

Area of Science:

Neuroscience
Molecular Biology
Pain Research

Background:

Nociceptive sensitization, characterized by allodynia and hyperalgesia, is a response to tissue damage.
Existing analgesics have limitations, necessitating the identification of novel pain targets.
Sensory neuron hypersensitivity underlies pain sensitization.

Purpose of the Study:

To investigate the role of Hedgehog (Hh) signaling in thermal nociceptive sensitization.
To explore Hh signaling's involvement in pain pathways in both Drosophila and mammals.
To identify potential therapeutic targets for pain management.

Main Methods:

Utilized a Drosophila model to study UV-induced thermal nociceptive sensitization.
Conducted genetic analysis to understand Hh signaling's interaction with TNF and TRP channels.
Administered cyclopamine (CP), a Sonic Hedgehog inhibitor, in rat models of inflammatory and neuropathic pain.

Main Results:

Hedgehog (Hh) signaling is essential for thermal allodynia and hyperalgesia in Drosophila following UV irradiation.
Hh signaling acts in parallel to tumor necrosis factor (TNF) signaling.
Distinct transient receptor potential (TRP) channels mediate allodynia and hyperalgesia downstream of Hh and TNF pathways.
Cyclopamine (CP) blocked analgesic tolerance to morphine and enhanced/sustained morphine analgesia in rats.

Conclusions:

Hedgehog (Hh) signaling plays a previously unrecognized role in nociception.
The findings reveal Hh signaling as a novel therapeutic target for pain treatment.
This research opens new avenues for developing improved pain management strategies.