Downregulation of Jun kinase signaling in the amnioserosa is essential fordorsal closure of the Drosophila embryo

Background: During Drosophila embryogenesis, Jun kinase (JNK) signaling has been shown to play a key role in regulating the morphogenetic process of d orsal closure, which also serves as a model for epithelial sheet fusion dur ing wound repair. During dorsal closure the JNK signaling cascade in the do rsal-most (leading edge) cells of the epidermis activates the AP-1 transcri ption factor comprised of DJUN and DFOS that, in turn, upregulates the expr ession of the dpp gene. DPP is a secreted morphogen that signals lateral ep idermal cells to elongate along the dorsoventral axis. The leading edge cel ls contact the peripheral cells of a monolayer extraembryonic epithelium, t he amnioserosa, which lies on the dorsal side of the embryo. Focal complexe s are present at the dorsal-most membrane of the leading edge cells, where they contact the amnioserosa. Results: We show that the JNK signaling cascade is initially active in both the amnioserosa and the leading edge of the epidermis. JNK signaling is do wnregulated in the amnioserosa, but not in the leading edge, prior to dorsa l closure. The subcellular localization of DFOS and DJUN is responsive to J NK signaling in the amnioserosa: JNK activation results in nuclear localiza tion of DFOS and DJUN; the downregulation of JNK signaling results in the r elocalization of DFOS and DJUN to the cytoplasm. The HINDSIGHT (HNT) Zn-fin ger protein and the PUCKERED (PUC) JNK phosphatase are essential for downre gulation of the JNK cascade in the amnioserosa. Persistent JNK activity in the amnioserosa. leads to defective focal complexes in the adjacent leading edge cells and to the failure of dorsal closure. Conclusions: Focal complexes are assembled at the boundary between high and low JNK activity. In the absence of focal complexes, miscommunication betw een the amnioserosa. and the leading edge may lead to a premature "stop" si gnal that halts dorsalward migration of the leading edge. Spatial and tempo ral regulation of the JNK signaling cascade may be a general mechanism that controls tissue remodeling during morphogenesis and wound healing.