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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

4.5K
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

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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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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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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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.
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...
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Diversity in Cell Signaling Responses01:22

Diversity in Cell Signaling Responses

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The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
Graded and Abrupt Responses
Some signaling systems generate...
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Cell Signaling Feedback Loops01:07

Cell Signaling Feedback Loops

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Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
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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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Related Experiment Video

Updated: Oct 3, 2025

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

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Multistability and transitions between spatiotemporal patterns through versatile Notch-Hes signaling.

Benjamin Pfeuty1

  • 1Univ. Lille, CNRS, UMR 8523 - PhLAM - Physique des Lasers Atomes et Molécules, F-59000 Lille, France.

Journal of Theoretical Biology
|February 17, 2022
PubMed
Summary

The Delta-Notch-Hes pathway

Keywords:
Cell-fate decisionMulticellular developmentMultistabilityOscillationsPattern formation

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Area of Science:

  • Developmental biology
  • Systems biology
  • Theoretical biology

Background:

  • The Delta-Notch-Hes signaling pathway regulates diverse developmental processes, including somite formation and tissue patterning.
  • Its broad patterning capabilities stem from the tunable dynamics of the Notch-Hes feedback circuit, exhibiting pulsatile and switching behaviors.
  • Understanding how lateral inhibition between cells with monostable, oscillatory, or bistable dynamics generates spatiotemporal patterns is a key theoretical challenge.

Purpose of the Study:

  • To investigate the spatiotemporal pattern formation arising from lateral inhibition in a model of the Delta-Notch-Hes pathway.
  • To determine how intracellular and intercellular parameters influence the stability and diversity of these patterns.
  • To explore the theoretical basis for robust and defect-free spatial pattern generation during development.

Main Methods:

  • A discrete cell lattice model was employed, with intracellular dynamics represented by a phase-like variable.
  • The model incorporates a cross-shaped phase diagram to describe cellular states.
  • Analysis focused on the dependence of spatially inhomogeneous and temporally synchronized states on model parameters.

Main Results:

  • The study reveals parameter-dependent multistability, where diverse spatiotemporal patterns coexist.
  • These patterns exhibit tunable and robust transition scenarios crucial for defect-free spatial patterning.
  • The findings are consistent with regulatory network modeling of the Delta-Notch-Hes pathway.

Conclusions:

  • The Delta-Notch-Hes pathway's broad spatiotemporal patterning capabilities arise from multistability within its feedback circuit.
  • Tunable intracellular and intercellular parameters allow for robust generation of complex developmental patterns.
  • This theoretical framework supports the understanding of how biological systems achieve precise spatial organization.