Cis-inhibition suppresses basal Notch signaling during sensory organ precursor selection

Tobias Troost, Udi Binshtok, David Sprinzak, Thomas Klein

Research output: Contribution to journalArticlepeer-review


The emergence of the sensory organ precursor (SOP) from an equivalence group in Drosophila is a paradigm for studying single-cell fate specification through Notch-mediated lateral inhibition. Yet, it remains unclear how only a single SOP is selected from a relatively large group of cells. We show here that a critical aspect of SOP selection is controlled by cis-inhibition (CI), whereby the Notch ligands, Delta (Dl), cis-inhibit Notch receptors in the same cell. Based on the observation that the mammalian ligand Dl-like 1 cannot cis-inhibit Notch in Drosophila, we probe the role of CI in vivo. We develop a mathematical model for SOP selection where Dl activity is independently regulated by the ubiquitin ligases Neuralized and Mindbomb1. We show theoretically and experimentally that Mindbomb1 induces basal Notch activity, which is suppressed by CI. Our results highlight the trade-off between basal Notch activity and CI as a mechanism for singling out a SOP from a large equivalence group.

Original languageEnglish
Article numbere2214535120
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - 2023


  • Delta-like-1
  • Notch signaling
  • cis-inhibition
  • neural precursor selection
  • neurogenesis

All Science Journal Classification (ASJC) codes

  • General


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