title: Apical deficiency triggers JNK-dependent apoptosis in the embryonic epidermis of Drosophila.
abstract: Epithelial homeostasis and the avoidance of diseases such as cancer require the elimination of defective cells by apoptosis. Here, we investigate how loss of apical determinants triggers apoptosis in the embryonic epidermis of Drosophila. Transcriptional profiling and in situ hybridisation show that JNK signalling is upregulated in mutants lacking Crumbs or other apical determinants. This leads to transcriptional activation of the pro-apoptotic gene reaper and to apoptosis. Suppression of JNK signalling by overexpression of Puckered, a feedback inhibitor of the pathway, prevents reaper upregulation and apoptosis. Moreover, removal of endogenous Puckered leads to ectopic reaper expression. Importantly, disruption of the basolateral domain in the embryonic epidermis does not trigger JNK signalling or apoptosis. We suggest that apical, not basolateral, integrity could be intrinsically required for the survival of epithelial cells. In apically deficient embryos, JNK signalling is activated throughout the epidermis. Yet, in the dorsal region, reaper expression is not activated and cells survive. One characteristic of these surviving cells is that they retain discernible adherens junctions despite the apical deficit. We suggest that junctional integrity could restrain the pro-apoptotic influence of JNK signalling.
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.
authors.forename: Golnar
authors.initials: G
authors.lastname: Kolahgar
authors.forename: Pierre-Luc
authors.initials: PL
authors.lastname: Bardet
authors.forename: Paul F
authors.initials: PF
authors.lastname: Langton
authors.forename: Cyrille
authors.initials: C
authors.lastname: Alexandre
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vincent
mesh_terms: D022005:Adherens Junctions / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D046228:Microarray Analysis; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C086973:rpr protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; C110854:puc protein, Drosophila; D010749:Phosphoprotein Phosphatases