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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...
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...
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...
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...
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...

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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
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Tissue-derived hedgehog proteins modulate Th differentiation and disease.

Anna L Furmanski1, Jose Ignacio Saldana, Masahiro Ono

  • 1Immunobiology Unit, Institute of Child Health, University College London, London WC1N 1EH, United Kingdom.

Journal of Immunology (Baltimore, Md. : 1950)
|February 15, 2013
PubMed
Summary

Tissue-derived Hedgehog (Hh) proteins influence T cell function, promoting allergic responses by driving Th2 differentiation. This study reveals a novel role for morphogens in regulating immune cells, suggesting new therapeutic targets for allergies and cancers.

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Area of Science:

  • Immunology
  • Developmental Biology
  • Molecular Biology

Background:

  • Complex immune-mediated diseases involve numerous low-risk genetic factors.
  • Tissue context significantly influences immune responses, particularly T cell function.
  • Hedgehog (Hh) proteins are known morphogens in tissue development but their role in immunity is unclear.

Purpose of the Study:

  • To investigate the role of tissue-derived molecules, specifically Hedgehog (Hh) proteins, in modulating T cell function.
  • To explore the impact of Hh signaling on T cell differentiation and immune responses.
  • To identify potential therapeutic targets for immune-mediated diseases.

Main Methods:

  • Analysis of Hh-dependent transcription in T cells.
  • Assessment of T cell differentiation and transcriptional programs.
  • Measurement of Sonic Hh expression in lung epithelial cells during allergic disease.
  • Investigation of Hh target gene expression in lung T cells in vivo.
  • Identification of Interleukin-4 (Il4) as a transcriptional target of Hh signaling.

Main Results:

  • Hh-dependent transcription in T cells promotes Th2 transcriptional programs and differentiation.
  • Allergic disease severity is exacerbated by Hh signaling in T cells.
  • Sonic Hh expression increases in lung epithelial cells during allergic disease.
  • Lung T cells upregulate Hh target gene expression in vivo, responding to local Hh ligands.
  • Interleukin-4 (Il4) is identified as a novel transcriptional target of Hh signals in T cells.

Conclusions:

  • Tissue-derived Hedgehog (Hh) proteins play a novel role in regulating fluid immune responses, particularly T cell function.
  • Hh signaling in T cells promotes Th2 differentiation and exacerbates allergic disease.
  • Hh secreted from inflamed or malignant tissues can modulate local T cell responses, offering potential for anti-Hh therapeutics in allergy and cancer.