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

Abstract

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.

Notch Signaling in Insect Development: A Simple Pathway with Diverse Functions

“…The selection of SOPs is governed by a lateral inhibition process orchestrated by Notch signaling. SOPs undergo stereotyped asymmetric divisions to form the mechanosensory organ and the fates of daughter cells are also regulated by Notch signaling [ 37 , 122 , 137 , 138 , 139 ]. A disruption of Notch activity at different developmental stages could disrupt bristle pattern and bristle number, as well as cell lineage specification [ 1 , 139 ].…”

Lepidopteran scale cells derive from sensory organ precursors through a canonical lineage

“…Similarities in histological changes between lepidopteran scales and mechanosensory bristles have prompted a few developmental studies of candidate genes involved in SOP lineage specification. The spatial definition of SOP clusters within the fly epithelium requires Notch (N) signalling to inhibit SOP fates (Troost et al, 2023). In early butterfly pupal wings, N is detected in rosettes of non-SOP epithelial cells, surrounding central SOP precursors that express low N (Reed, 2004).…”