Notch and Prospero repress proliferation following cyclin E overexpression in the Drosophila bristle lineage

Françoise Simon1, Pierre Fichelson, Michel Gho

  • 1Université Pierre et Marie Curie-Paris 6, UMR 7622, Paris, France.

Plos Genetics
|August 8, 2009
PubMed

Insights

Post-mitotic cells in adult flies can re-enter the cell cycle when cyclin E is overexpressed. Cell cycle re-entry depends on cell identity, specifically Notch pathway activity and Prospero, regulating differentiation.

Area of Science:

  • Developmental Biology
  • Cell Cycle Regulation
  • Drosophila melanogaster research

Background:

  • Coordinating cell proliferation, arrest, and differentiation is key to understanding normal and pathological development.
  • The adult fly bristle lineage provides a model to study cell cycle control in post-mitotic cells.

Purpose of the Study:

  • To investigate the capacity of post-mitotic cells to re-enter the cell cycle.
  • To determine the factors influencing cell cycle re-entry upon cyclin E overexpression.

Main Methods:

  • Overexpression of cyclin E in the adult fly bristle lineage.
  • Analysis of cell division and differentiation markers.
  • Assessing the role of Notch pathway activity and Prospero.

Main Results:

  • Terminal cells independent of the Notch pathway divided upon cyclin E overexpression.
  • Cellular responsiveness to forced proliferation is modulated by Prospero and Notch pathway activity.
  • Two parallel mechanisms regulate terminal quiescence, differentiation, fate acquisition, and cell cycle progression.

Conclusions:

  • Cellular fate and cell cycle progression are regulated by parallel mechanisms.
  • Notch pathway activity and Prospero are critical regulators of cell cycle re-entry in differentiating cells.

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...