title: The co-regulator dNAB interacts with Brinker to eliminate cells with reduced Dpp signaling.
abstract: The proper development of tissues requires morphogen activity that dictates the appropriate growth and differentiation of each cell according to its position within a developing field. Elimination of underperforming cells that are less efficient in receiving/transducing the morphogenetic signal is thought to provide a general fail-safe mechanism to avoid developmental misspecification. In the developing Drosophila wing, the morphogen Dpp provides cells with growth and survival cues. Much of the regulation of transcriptional output by Dpp is mediated through repression of the transcriptional repressor Brinker (Brk), and thus through the activation of target genes. Mutant cells impaired for Dpp reception or transduction are lost from the wing epithelium. At the molecular level, reduced Dpp signaling results in Brk upregulation that triggers apoptosis through activation of the JNK pathway. Here we show that the transcriptional co-regulator dNAB is a Dpp target in the developing wing that interacts with Brk to eliminate cells with reduced Dpp signaling through the JNK pathway. We further show that both dNAB and Brk are required for cell elimination induced by differential dMyc expression, a process that depends on reduced Dpp transduction in outcompeted cells. We propose a novel mechanism whereby the morphogen Dpp regulates the responsiveness to its own survival signal by inversely controlling the expression of a repressor, Brk, and its co-repressor, dNAB.
authors.affiliation: Developmental Biology and Cancer Research, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Ziv
authors.forename: Yaron
authors.initials: Y
authors.lastname: Suissa
authors.forename: Hadar
authors.initials: H
authors.lastname: Neuman
authors.forename: Tama
authors.initials: T
authors.lastname: Dinur
authors.forename: Peter
authors.initials: P
authors.lastname: Geuking
authors.forename: Christa
authors.initials: C
authors.lastname: Rhiner
authors.forename: Marta
authors.initials: M
authors.lastname: Portela
authors.forename: Fidel
authors.initials: F
authors.lastname: Lolo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Moreno
authors.forename: Offer
authors.initials: O
authors.lastname: Gerlitz
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D017344:Genes, Insect; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D012097:Repressor Proteins; C490626:NAB protein, Drosophila; C118082:brk protein, Drosophila; C064196:dpp protein, Drosophila; C091023:gro protein, Drosophila