title: Cis-interactions between Notch and its ligands block ligand-independent Notch activity.
abstract: The Notch pathway is integrated into numerous developmental processes and therefore is fine-tuned on many levels, including receptor production, endocytosis, and degradation. Notch is further characterized by a twofold relationship with its Delta-Serrate (DSL) ligands, as ligands from opposing cells (trans-ligands) activate Notch, whereas ligands expressed in the same cell (cis-ligands) inhibit signaling. We show that cells without both cis- and trans-ligands can mediate Notch-dependent developmental events during Drosophila oogenesis, indicating ligand-independent Notch activity occurs when the receptor is free of cis- and trans-ligands. Furthermore, cis-ligands can reduce Notch activity in endogenous and genetically induced situations of elevated trans-ligand-independent Notch signaling. We conclude that cis-expressed ligands exert their repressive effect on Notch signaling in cases of trans-ligand-independent activation, and propose a new function of cis-inhibition which buffers cells against accidental Notch activity.
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, United States.
authors.forename: William Hunt
authors.initials: WH
authors.lastname: Palmer
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, United States.
authors.forename: Dongyu
authors.initials: D
authors.lastname: Jia
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, United States.
authors.forename: Wu-Min
authors.initials: WM
authors.lastname: Deng
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004330:Drosophila; D008024:Ligands; D009866:Oogenesis; D011485:Protein Binding; D034622:RNA Interference; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D008024:Ligands; D051880:Receptors, Notch
keywords: D. melanogaster; Notch pathway; cell biology; developmental biology; oogenesis; signal transduction; stem cells