A Wingless and Notch double-repression mechanism regulates G1-S transition in the Drosophila wing

Héctor Herranz1, Lidia Pérez, Francisco A Martín

  • 1ICREA and Institute for Research in Biomedicine, Barcelona, Spain.

The EMBO Journal
|May 3, 2008
PubMed

Insights

Wnt/Wingless (Wg) and Notch signaling pathways control tissue growth. This study reveals they act linearly to regulate cell cycle progression by modulating dmyc and bantam microRNA, impacting cancer development.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Cancer Biology

Background:

  • Tissue growth and patterning rely on Wnt/Wingless (Wg) and Notch signaling pathways.
  • Mutations in these pathways are linked to cancer, but their precise roles in cell proliferation and pathway crosstalk are unclear.
  • Previous research suggested Notch and Wg crosstalk organizes pattern and growth in Drosophila wing development.

Purpose of the Study:

  • To elucidate the linear pathway and molecular mechanisms by which Wnt/Wingless (Wg) and Notch signaling control cell-cycle progression.
  • To investigate the roles of dmyc proto-oncogene and bantam micro-RNA in this pathway.
  • To understand how Notch and Wg signaling influence G1-S progression in Drosophila wing cells.

Main Methods:

  • Investigated the signaling interactions between Wnt/Wingless (Wg) and Notch pathways in Drosophila wing primordia.
  • Analyzed the regulation of dmyc proto-oncogene and bantam micro-RNA expression by Wg and Notch.
  • Assessed the impact of these molecules on E2F transcription factor activity and G1-S cell-cycle progression.

Main Results:

  • Wnt/Wingless (Wg) and Notch signaling function in a linear pathway to control G1-S cell-cycle progression.
  • Wg and Notch regulate the expression of dmyc and bantam micro-RNA.
  • These molecules positively modulate E2F transcription factor activity, with Notch repressing cell-cycle progression and Wg alleviating this repression.

Conclusions:

  • Notch signaling acts as a repressor of cell-cycle progression in Drosophila wing cells.
  • Wnt/Wingless (Wg) signaling plays a permissive role, relieving Notch-mediated repression of G1-S progression.
  • The coordinated action of Wg, Notch, dmyc, and bantam micro-RNA is crucial for controlling cell proliferation and tissue patterning.

Related Concept Videos

The Ratio of X Chromosome to Autosomes02:45

The Ratio of X Chromosome to Autosomes

In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.  
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
Position-effect Variegation02:32

Position-effect Variegation

In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
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...
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...
Dosage Compensation02:50

Dosage Compensation

In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with  distinct numbers of X chromosomes will have...
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.