Down-regulation of Notch signaling during corneal epithelial proliferation

A R Djalilian1, A Namavari, A Ito

  • 1Department of Ophthalmology, University of Illinois at Chicago, Chicago, IL 60612, USA. adjalili@uic.edu <adjalili@uic.edu>

Molecular Vision
|June 17, 2008
PubMed
Abstract

Insights

Notch pathway genes are expressed in the corneal epithelium, with differing levels in limbal versus central areas. Notch signaling inversely correlates with corneal epithelial proliferation, suggesting a role in differentiation.

Area of Science:

  • Ophthalmology
  • Developmental Biology
  • Cell Biology

Background:

  • The corneal epithelium maintains transparency and undergoes continuous renewal.
  • Notch signaling is a critical pathway regulating cell fate and differentiation in various tissues.

Purpose of the Study:

  • To investigate the expression and activation of Notch pathway genes in the adult human and murine corneal epithelium during proliferation.
  • To understand the role of Notch signaling in corneal epithelial homeostasis and differentiation.

Main Methods:

  • Reverse transcription polymerase chain reaction (RT-PCR) to assess gene expression.
  • Immunofluorescence and in situ hybridization to examine expression patterns.
  • Western blot for Notch intracellular domain (NotchIC) to determine Notch activity.
  • Murine wound healing models and in vitro cell culture experiments.

Main Results:

  • Notch1 and Jagged1 expression was higher in human limbal epithelium, while Hes1 and Hes5 were higher in the central cornea.
  • Notch pathway gene expression was localized to basal and suprabasal cells.
  • Notch intracellular domain levels decreased during wound healing and with phorbol myristate application.
  • Hes1 expression increased in confluent cells under high calcium conditions in vitro.

Conclusions:

  • Notch signaling exhibits an inverse correlation with the proliferative status of the corneal epithelium.
  • These findings support the role of Notch signaling in regulating corneal epithelial differentiation.

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

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 until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

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 until 1985...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

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...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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 results in tumor...