Common and distinct roles of DFos and DJun during Drosophila development

The Drosophila homolog of c-Jun regulates epithelial cell shape changes during the process of dorsal closure in mid-embryogenesis. Here, mutations in the DFos gene are described. In dorsal closure, DFos cooperates with DJun by regulating the expression of dpp; Dpp acts as a relay signal that triggers cell shape changes and DFos expression in neighboring cells. In addition to the joint requirement of DFos and DJun during dorsal closure, DFos functions independently of DJun during early stages of embryogenesis. These findings demonstrate common and distinct roles of DFos and DJun during em-bryogenesis and suggest a conserved link between AP-1 (activating protein-1) and TGF-b (transforming growth factor–b) signaling during epithelial cell shape changes. The AP-1 transcription factor complex is activated in response to various stimuli, including cytokines, growth factors, and cellular stresses like ultraviolet irradiation or heat shock. Active AP-1 complexes are dimers of basic-region leucine zipper (bZip) transcription factors, formed predominantly by members of the Jun and Fos gene families (1). In vertebrates, the number of related Jun and Fos family members has complicat-ed analysis of AP-1 function in vivo. c-fos mutant mice are viable and possess defects in bone formation, whereas c-jun mutant mice die at mid-gestation with liver defects (2). In Drosophila, single homologs of c-Jun and c-Fos, DJun and DFra (here referred to as DFos), have been identified (3, 4). Like c-Jun, DJun forms homodimers and het-erodimers with DFos and binds to AP-1 DNA binding sites. In contrast to mamma-lian c-Fos, however, DFos also forms ho-modimers, suggesting DJun-independent functions (3). DJun mutant embryos die as a result of failed dorsal closure (5–7). Dorsal closure occurs during mid-embryogenesis and results in stretching of the lateral epi-thelia over the extraembryonic membrane and fusion at the dorsal mid-line. In addi-tion to DJun, mutations in genes encoding Jun NH2-terminal kinase kinase (DJNKK), hep, and Jun NH2-terminal kinase (DJNK), bsk, also block this cell shape change, and thus, dorsal closure (8–10). Expression of dpp in the most dorsal row of cells, the leading edge, is dependent on DJun, DJNK