Novel Notch alleles reveal a Deltex-dependent pathway repressing neural fate

Curr Biol. 2001 Nov 13;11(22):1729-38. doi: 10.1016/s0960-9822(01)00562-0.

Abstract

Background: The Notch receptor triggers a wide range of cell fate choices in higher organisms. In Drosophila, segregation of neural from epidermal lineages results from competition among equivalent cells. These cells express achaete/scute genes, which confer neural potential. During lateral inhibition, a single neural precursor is selected, and neighboring cells are forced to adopt an epidermal fate. Lateral inhibition relies on proteolytic cleavage of Notch induced by the ligand Delta and translocation of the Notch intracellular domain (NICD) to the nuclei of inhibited cells. The activated NICD, interacting with Suppressor of Hairless [Su(H)], stimulates genes of the E(spl) complex, which in turn repress the proneural genes achaete/scute.

Results: Here, we describe new alleles of Notch that specifically display loss of microchaetae sensory precursors. This phenotype arises from a repression of neural fate, by a Notch signaling distinct from that involved in lateral inhibition. We show that the loss of sensory organs associated with this phenotype results from a constitutive activation of a Deltex-dependent Notch-signaling event. These novel Notch alleles encode truncated receptors lacking the carboxy terminus of the NICD, which is the binding site for the repressor Dishevelled (Dsh). Dsh is known to be involved in crosstalk between Wingless and Notch pathways.

Conclusions: Our results reveal an antineural activity of Notch distinct from lateral inhibition mediated by Su(H). This activity, mediated by Deltex (Dx), represses neural fate and is antagonized by elements of the Wingless (Wg)-signaling cascade to allow alternative cell fate choices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alleles*
  • Animals
  • Binding Sites
  • Cell Differentiation
  • Dishevelled Proteins
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins*
  • Glycogen Synthase Kinase 3*
  • Insect Proteins / genetics
  • Insect Proteins / metabolism*
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mutagenesis
  • Neurons / cytology*
  • Neurons / metabolism
  • Phenotype
  • Phosphoproteins / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Notch
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Wnt1 Protein

Substances

  • Adaptor Proteins, Signal Transducing
  • DX protein, Drosophila
  • Dishevelled Proteins
  • Drosophila Proteins
  • Insect Proteins
  • Membrane Proteins
  • N protein, Drosophila
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Receptors, Notch
  • Repressor Proteins
  • Su(H) protein, Drosophila
  • Wnt1 Protein
  • dsh protein, Drosophila
  • wg protein, Drosophila
  • Protein Serine-Threonine Kinases
  • Sgg protein, Drosophila
  • Glycogen Synthase Kinase 3