The Drosophila serine protease homologue Scarface regulates JNK signalling in a negative-feedback loop during epithelial morphogenesis.
In Drosophila melanogaster, dorsal closure is a model of tissue morphogenesis leading to the dorsal migration and sealing of the embryonic ectoderm. The activation of the JNK signal transduction pathway, specifically in the leading edge cells, is essential to this process. In a genome-wide microarray screen, we identified new JNK target genes during dorsal closure. One of them is the gene scarface (scaf), which belongs to the large family of trypsin-like serine proteases. Some proteins of this family, like Scaf, bear an inactive catalytic site, representing a subgroup of serine protease homologues (SPH) whose functions are poorly understood. Here, we show that scaf is a general transcriptional target of the JNK pathway coding for a secreted SPH. scaf loss-of-function induces defects in JNK-controlled morphogenetic events such as embryonic dorsal closure and adult male terminalia rotation. Live imaging of the latter process reveals that, like for dorsal closure, JNK directs the dorsal fusion of two epithelial layers in the pupal genital disc. Genetic data show that scaf loss-of-function mimics JNK over-activity. Moreover, scaf ectopic expression aggravates the effect of the JNK negative regulator puc on male genitalia rotation. We finally demonstrate that scaf acts as an antagonist by negatively regulating JNK activity. Overall, our results identify the SPH-encoding gene scaf as a new transcriptional target of JNK signalling and reveal the first secreted regulator of the JNK pathway acting in a negative-feedback loop during epithelial morphogenesis.
University of Nice Sophia-Antipolis, UMR 6543 CNRS, Institute of Developmental Biology and Cancer, Parc Valrose, 06108 Nice CEDEX2, France.
Raphaël
R
Rousset
Sophie
S
Bono-Lauriol
Melanie
M
Gettings
Magali
M
Suzanne
Pauline
P
Spéder
Stéphane
S
Noselli
D000818:Animals; D004331:Drosophila melanogaster / Q000196:embryology* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005246:Feedback; D005837:Genitalia, Male / Q000196:embryology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D009024:Morphogenesis; D015398:Signal Transduction
D048031:JNK Mitogen-Activated Protein Kinases