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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

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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.
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...
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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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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.
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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Non-Canonical Wnt Signaling Pathways01:41

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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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Canonical Wnt Signaling Pathway02:54

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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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Amplifying Signals via Enzymatic Cascade01:22

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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Hedgehog Signaling Pathway02:33

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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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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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Neuralized-like proteins differentially activate Notch ligands.

Alina Airich1, Oren Gozlan2, Ekaterina Seib1

  • 1Institut fuer Genetik, Heinrich-Heine-Universtitaet Duesseldorf, Universitaetstr. 1, 40225, Duesseldorf, Germany.

EMBO Reports
|November 1, 2025
PubMed
Summary
This summary is machine-generated.

Neuralized-like (NEURL) proteins regulate mammalian Notch signalling differently than in flies. NEURL proteins activate only specific Notch ligands (DLL1 and JAG1) containing a Neuralized binding motif, explaining their limited developmental role.

Keywords:
DSL ligandsE3 ubiquitin ligasesNeuralizedNotch signalling

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

  • Cellular biology
  • Developmental biology
  • Molecular signalling

Background:

  • Notch signalling coordinates cellular processes in animals.
  • Neuralized (Neur) and Mindbomb1 (Mib1) E3 ubiquitin ligases regulate Notch in Drosophila.
  • Mammalian NEURL proteins appear dispensable for development, raising questions about their function.

Purpose of the Study:

  • Investigate how NEURL proteins regulate mammalian Notch ligands.
  • Determine if NEURL proteins exhibit differential ligand activation.
  • Clarify the role of NEURL proteins in mammalian development and homeostasis.

Main Methods:

  • Utilized a humanized Drosophila model to study NEURL protein function.
  • Employed mammalian cell culture systems for analysis.
  • Examined Notch ligand activation by NEURL proteins and identified a specific binding motif.

Main Results:

  • NEURL proteins activate a subset of mammalian Notch ligands, unlike MIB1.
  • Ligand activation by NEURL is dependent on the presence of a Neuralized binding motif (NxxN).
  • DLL1 and JAG1 ligands contain this motif, while DLL4 and JAG2 do not.

Conclusions:

  • Mammalian Notch activation exhibits differential regulation by NEURL proteins.
  • The presence of the Neuralized binding motif dictates NEURL-mediated ligand activation.
  • This differential mechanism may explain the limited in vivo role of NEURL proteins in mammalian development.