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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.
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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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Chromatin Modification in iPS Cells01:32

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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
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Related Experiment Video

Updated: Mar 22, 2026

Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
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The chromatin modifying complex CoREST/LSD1 negatively regulates notch pathway during cerebral cortex development.

Cecilia I Lopez1,2, Katherine E Saud1,2, Rodrigo Aguilar3

  • 1Faculty of Medicine, Program in Physiology and Biophysics, Institute for Biomedical Sciences, Universidad de Chile, Santiago, Chile.

Developmental Neurobiology
|April 27, 2016
PubMed
Summary
This summary is machine-generated.

Epigenetic modulators CoREST and lysine-specific demethylase 1 (LSD1) regulate Notch pathway activity in the developing brain. These proteins downregulate Notch signaling, impacting neural stem cell differentiation and neuronal migration.

Keywords:
cerebral cortexdevelopmentdifferentiationepigeneticneurogenesis

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Epigenetics

Background:

  • Cerebral cortex development requires precise regulation of cell division, death, migration, and differentiation.
  • The Notch pathway is crucial for maintaining neural stem cell pools and regulating differentiation.

Purpose of the Study:

  • Investigate the role of epigenetic modulators lysine-specific demethylase 1 (LSD1) and CoREST in regulating Notch pathway activity during cerebral cortex development.
  • Determine how LSD1 and CoREST interact with the Notch pathway and influence neural stem cell behavior.

Main Methods:

  • In vitro interaction studies of CoREST, LSD1, and RBPJ-κ.
  • In utero electroporation to knock down CoREST and LSD1 in developing cerebral cortex.
  • Analysis of gene expression (Hes1, Ngn2) and cell markers (Sox2, Tbr2).
  • Assessment of neuronal migration defects.

Main Results:

  • CoREST and LSD1 interact with RBPJ-κ in a repressor complex, released upon Notch intracellular domain (NICD) overexpression.
  • LSD1 binds to the Hes1 promoter; knock-down of CoREST/LSD1 increases Hes1 and decreases Ngn2 expression.
  • CoREST/LSD1 knock-down causes neuronal migration defects and increases Sox2/Tbr2 expressing cells, effects reversed by Notch pathway loss.

Conclusions:

  • CoREST and LSD1 function to downregulate the Notch pathway in the developing cerebral cortex.
  • Epigenetic regulation by CoREST and LSD1 plays a critical role in fine-tuning neural cell differentiation.
  • Findings suggest a novel mechanism linking epigenetic modifiers to Notch signaling in brain development.