title: Insensitive is a corepressor for Suppressor of Hairless and regulates Notch signalling during neural development.
abstract: The Notch intracellular domain functions as a co-activator for the DNA-binding protein Suppressor of Hairless (Su(H)) to mediate myriad cell fate decisions. Notch pathway activity is balanced by transcriptional repression, mediated by Su(H) in concert with its Drosophila corepressor Hairless. We demonstrate that the Drosophila neural BEN-solo protein Insensitive (Insv) is a nuclear factor that inhibits Notch signalling during multiple peripheral nervous system cell fate decisions. Endogenous Insv was particularly critical when repressor activity of Su(H) was compromised. Reciprocally, ectopic Insv generated several Notch loss-of-function phenotypes, repressed most Notch targets in the E(spl)-C, and opposed Notch-mediated activation of an E(spl)m3-luc reporter. A direct role for Insv in transcriptional repression was indicated by binding of Insv to Su(H), and by strong chromatin immunoprecipitation of endogenous Insv to most E(spl)-C loci. Strikingly, ectopic Insv fully rescued sensory organ precursors in Hairless null clones, indicating that Insv can antagonize Notch independently of Hairless. These data shed first light on the in vivo function for a BEN-solo protein as an Su(H) corepressor in the Notch pathway regulating neural development.
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, New York, NY, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Duan
authors.forename: Qi
authors.initials: Q
authors.lastname: Dai
authors.forename: Joshua
authors.initials: J
authors.lastname: Kavaler
authors.forename: Fernando
authors.initials: F
authors.lastname: Bejarano
authors.forename: Giorgio
authors.initials: G
authors.lastname: Medranda
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nègre
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
mesh_terms: D000818:Animals; D056970:Co-Repressor Proteins / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D009024:Morphogenesis; D009420:Nervous System / Q000196:embryology*; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D056970:Co-Repressor Proteins; D029721:Drosophila Proteins; C561461:Insv protein, Drosophila; C497759:N protein, Drosophila; D051880:Receptors, Notch; D012097:Repressor Proteins; C088731:Su(H) protein, Drosophila