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Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

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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...
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Notch Signaling Pathway03:14

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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.
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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
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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.
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
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Related Experiment Video

Updated: Aug 10, 2025

Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
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Hedgehog is relayed through dynamic heparan sulfate interactions to shape its gradient.

Fabian Gude1, Jurij Froese1, Dominique Manikowski1

  • 1From the Institute for Physiological Chemistry and Pathobiochemistry, University of Münster, 48149, Münster, Germany.

Nature Communications
|February 10, 2023
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Hedgehog (Hh) morphogen spreading, crucial for development, relies on Hh molecules cross-linking heparan sulfate (HS) chains. This interaction controls Hh gradient formation, revealing a scalable design principle in patterned tissues.

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Area of Science:

  • Developmental biology
  • Molecular biology
  • Biochemistry

Background:

  • Cellular differentiation depends on morphogen concentration gradients.
  • Hedgehog (Hh) morphogens are key to pattern formation in Drosophila development.
  • The mechanism of extracellular Hh spread and precise gradient formation remains unclear.

Purpose of the Study:

  • To elucidate the mechanism of extracellular Hedgehog (Hh) morphogen spread.
  • To understand how Hh spread translates into precise morphogen gradients.
  • To identify the role of heparan sulfate (HS) interactions in Hh gradient formation.

Main Methods:

  • Investigated Hh-heparan sulfate (HS) interactions using in vitro assays.
  • Utilized mutated Hh variants with altered binding sites.
  • Analyzed Hh gradient formation in vivo in Drosophila models.

Main Results:

  • Hh molecules possess two binding areas that simultaneously interact with two HS chains, forming temporary cross-links.
  • Hh mutants with impaired binding sites showed reduced HS cross-linking.
  • Reduced HS cross-linking in mutants led to impaired Hh switching and altered Hh gradients in vivo.

Conclusions:

  • Direct Hh switching between HS chains is essential for shaping Hh gradients.
  • The speed and propensity of Hh switching on HS chains represent a scalable design principle for morphogen gradients.
  • This mechanism provides new insights into morphogen transport and tissue patterning.