Different modes of Notch activation and strength regulation in the spermathecal secretory lineage

Development. 2020 Feb 7;147(3):dev184390. doi: 10.1242/dev.184390.

Abstract

The strength of Notch signaling contributes to pleiotropic actions of Notch; however, we do not yet have a full understanding of the molecular regulation of Notch-signaling strength. We have investigated the mode of Notch activation in binary fate specification in the Drosophila spermathecal linage, where Notch is asymmetrically activated across three divisions to specify different cell fates. Using clonal analysis, we show that Delta (Dl) serves as the ligand for Notch in the first and second divisions. Dl and Serrate (Ser) function redundantly in the third division. Compared with the third division, cell-fate decision in the second division requires a lower level of Suppressor of Hairless protein, and, consequently, a lower level of Notch signaling. Several Notch endosomal trafficking regulators differentially regulate Notch signaling between the second and third divisions. Here, we demonstrate that cell differentiation in spermathecae involves different Notch-activation modes, Notch-signaling strengths and Notch-trafficking regulations. Thus, the Drosophila spermathecal lineage is an exciting model for probing the molecular mechanisms that modulate the Notch signaling pathway.

Keywords: Asymmetric Notch activation; Deltex; Notch signaling strength; Numb; Rab5.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Cell Lineage / genetics*
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Endosomes / metabolism
  • Female
  • Gene Knockdown Techniques
  • Genitalia / cytology*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Jagged-1 Protein / genetics
  • Jagged-1 Protein / metabolism
  • Ligands
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Repressor Proteins / metabolism
  • Signal Transduction

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • Ligands
  • Membrane Proteins
  • N protein, Drosophila
  • Receptors, Notch
  • Repressor Proteins
  • Ser protein, Drosophila
  • Su(H) protein, Drosophila
  • delta protein