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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

4.3K
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...
4.3K
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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Notch pathway mutants do not equivalently perturb mouse embryonic retinal development.

Bernadett Bosze1, Julissa Suarez-Navarro1, Illiana Cajias1

  • 1Department of Cell Biology & Human Anatomy, University of California, Davis, California, United States of America.

Plos Genetics
|September 26, 2023
PubMed
Summary

Notch signaling guides retinal progenitor cell fate by regulating Hes genes. This study reveals Hes1 acts as a crucial hub, integrating Notch-dependent and -independent signals for eye development.

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Ophthalmology

Background:

  • Notch signaling is crucial for vertebrate retinal progenitor cell fate determination, primarily through Hes effector genes.
  • Developmental complexity arises from redundant and compensatory mechanisms involving multiple paralogues in the Notch pathway.
  • Understanding these intricate regulatory networks is essential for dissecting early eye development.

Purpose of the Study:

  • To investigate the role of the Notch ternary complex and Hes genes in optic stalk/nerve head development.
  • To determine Notch-dependent and -independent functions of intracellular pathway components in retinal ganglion cell and cone photoreceptor development.
  • To elucidate the complexity of Notch signaling and Hes gene activity in early vertebrate eye development.

Main Methods:

  • Utilized seven germline or conditional mutant mouse models.
  • Employed two spatiotemporally distinct Cre drivers for targeted gene manipulation.
  • Perturbed the Notch ternary complex and multiple Hes genes to analyze their effects.

Main Results:

  • Disruption of Notch signaling universally inhibits progenitor cell proliferation.
  • Identified specific pathway components, like Hes1, exhibiting Notch-independent roles in the optic stalk/nerve head.
  • Observed that Hes genes do not uniformly suppress retinal ganglion cell or cone differentiation in retinal progenitor cells.
  • Found correlations between early cell fate shifts and Otx2 expression, but not Atoh7.
  • Defined multiple roles for Rbpj and Hes1 during photoreceptor genesis, including redundant downstream activities.

Conclusions:

  • Hes1 acts as a central hub, integrating both Notch-dependent and -independent signals.
  • Hes1 plays unique roles at the retina-optic stalk boundary and in cone photoreceptor genesis.
  • The study clarifies the complex interplay of Notch signaling and Hes genes in regulating cell fate during eye development.