title: Inhibition of a NF-κB/Diap1 Pathway by PGRP-LF Is Required for Proper Apoptosis during Drosophila Development.
abstract: NF-κB pathways are key signaling cascades of the Drosophila innate immune response. One of them, the Immune Deficiency (IMD) pathway, is under a very tight negative control. Although molecular brakes exist at each step of this signaling module from ligand availability to transcriptional regulation, it remains unknown whether repressors act in the same cells or tissues and if not, what is rationale behind this spatial specificity. We show here that the negative regulator of IMD pathway PGRP-LF is epressed in ectodermal derivatives. We provide evidence that, in the absence of any immune elicitor, PGRP-LF loss-of-function mutants, display a constitutive NF-κB/IMD activation specifically in ectodermal tissues leading to genitalia and tergite malformations. In agreement with previous data showing that proper development of these structures requires induction of apoptosis, we show that ectopic activation of NF-κB/IMD signaling leads to apoptosis inhibition in both genitalia and tergite primordia. We demonstrate that NF-κB/IMD signaling antagonizes apoptosis by up-regulating expression of the anti-apoptotic protein Diap1. Altogether these results show that, in the complete absence of infection, the negative regulation of NF-κB/IMD pathway by PGRP-LF is crucial to ensure proper induction of apoptosis and consequently normal fly development. These results highlight that IMD pathway regulation is controlled independently in different tissues, probably reflecting the different roles of this signaling cascade in both developmental and immune processes.
authors.affiliation: Aix Marseille Univ, CNRS, IBDM, Marseille, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Tavignot
authors.affiliation: Aix Marseille Univ, CNRS, IBDM, Marseille, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Chaduli
authors.affiliation: Aix Marseille Univ, CNRS, IBDM, Marseille, France.
authors.forename: Fatoumata
authors.initials: F
authors.lastname: Djitte
authors.affiliation: Aix Marseille Univ, CNRS, IBDM, Marseille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Charroux
authors.affiliation: Aix Marseille Univ, CNRS, IBDM, Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Royet
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D004475:Ectoderm / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005835:Genitalia / Q000254:growth & development / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; C118897:peptidoglycan recognition protein