In the March 24 issue of Science, a flurry of papers report on the impending completion of the Drosophila melanogaster genome sequence. This historic achievement is the result of a unique collaboration between the Berkeley Drosophila Genome Project (BDGP), led by Gerry Rubin, and the genomics company Celera, headed by Craig Venter. With its genome almost completely sequenced ahead of schedule, Drosophila is another important model organism to enter the postgenomic age, and represents the largest genome sequenced to date.

Heparan sulfate proteoglycans (HSPGs) are associated with the cell surface and covalently linked to a small number of long unbranched chains of repeating disaccharides. Numerous biochemical studies of these extracellular matrix molecules have implicated them in a variety of biological phenomena, in particular cell-cell interactions. Recent genetic studies in Drosophila have begun to clarify the function of HSPGs in vivo and recent findings have implicated HSPGs in Wnt, Hedgehog, fibroblast growth factor and transforming growth factor-beta signaling pathways during development.

Heparan sulfate proteoglycans (HSPGs) are abundant molecules associated with the cell surface and extracellular matrix, and consist of a protein core to which heparan sulfate (HS) glycosaminoglycan (GAG) chains are attached. Although these molecules have been the focus of intense biochemical studies in vitro, their biological functions in vivo were unclear until recently. We have undertaken an in vivo functional study of HSPGs in Drosophila. Our studies, as well as others, demonstrate the critical roles of HSPGs in several major signaling pathways, including ibroblast growth factor (FGF), Wnt, Hedgehog (Hh) and TGF-beta. Our results also suggest that specific HS GAG chain modifications, as well as specific HSPG protein cores, are involved in specific signaling pathways.

The JAK/STAT signal transduction pathway has been conserved throughout evolution such that true structural and functional homologues of components originally identified in vertebrate systems are also present in the model genetic system Drosophila melanogaster. In addition to roles during larval hematopoiesis reminiscent of the requirement for this pathway in mammalian systems, the JAK/STAT pathway in Drosophila is also involved in a number of other developmental events. Recent data has demonstrated further roles for the JAK/STAT pathway in the establishment of sexual identity via the early embryonic expression of Sex lethal, the segmentation of the embryo via the control of pair rule genes including even skipped and the establishment of polarity within the adult compound eye via a mechanism that includes the four jointed gene. Use of the powerful genetics in the model organism Drosophila may identify new components of the JAK/STAT pathway, define new roles for this pathway, and provide insights into the function of this signal transduction system. Here we review the roles of STAT and its associated signaling pathway during both embryonic and adult stages of Drosophila development and discuss future prospects for the identification and characterization of novel pathway components and targets. Oncogene (2000).

The Drosophila JAK-STAT pathway and its ligand Unpaired are required for a wide range of developmental processes. Recent results have identified Unpaired as an activator of sex-lethal and revealed a new role for the JAK-STAT pathway in sex determination.

Do different signaling pathways inside the same cell talk to each other? Evidence suggests that in the worm and fly, signaling pathways exist as separate linear cassettes, whereas in mammalian cells there does appear to be cross talk between signaling pathways. However, as Noselli and Perrimon argue in their Perspective, most of the evidence in mammalian cells comes from tumor cells and overexpression assays. They suggest that true cross talk may not actually exist in mammalian cells under normal circumstances.   

Heparan sulphate proteoglycans are abundant cell-surface molecules that consist of a protein core to which heparan sulphate glycosaminoglycan chains are attached. The functions of these molecules have remained mostly underappreciated by developmental biologists; however, the actions of important signalling molecules, for example Wnt and Hedgehog, depend on them. To understand both the mechanisms by which ligands involved in development interact with their receptors and how morphogens pattern tissues, biologists need to consider the functions of heparan sulphate proteoglycans in signalling and developmental patterning.

Cells commonly use multiprotein kinase cascades to signal information from the cell membrane to the nucleus. Several conserved signaling pathways related to the mitogen activated protein kinase (MAPK) pathway allow cells to respond to normal developmental signals as well as signals produced under stressful conditions. Genetic and molecular studies in Drosophila melanogaster over the last several years have related that components of stress signaling pathways, namely the Jun kinase (JNK) and p38 kinase signaling modules, are functionally conserved and participate in numerous processes during normal development. Specifically, the JNK pathway is required for morphogenetic movements in embryogenesis and generation of tissue polarity in the adult. The role of the p38 pathway in generation of axial polarity during oogenesis has been inferred from phenotypic analysis of mutations in the Drosophila homolog of DMKK3. In addition to their requirement for normal development, cell culture and genetic investigations point to a role for both the JNK and p38 pathways in regulation of the immune response in the fly. This review details the known components of stress signaling pathways in Drosophila and recent insights into how these pathways are used and regulated during development and homeostasis.

The ability to create mosaic animals allows the phenotypic analysis of patches of groups of genetically different cells that develop in a wild type environment. In Drosophila, a variety of techniques have been developed over the years to generate mosaics, and in this chapter, I review the techniques that our laboratory has developed. These include the "Dominant Female Sterile" technique which allows the analysis of gene functions to oogenesis and embryogenesis; the "Gal4-UAS" technique which allows the control of where and when specific genes are expressed; and, the "Positive Marked Mutant Lineages" technique which allows clones of cells to express a specific reporter gene.

Within the last three years, Frizzled receptors have risen from obscurity to celebrity status owing to their functional identification as receptors for the ubiquitous family of secreted WNT signaling factors. However, the founding member of the Frizzled family, Drosophila Frizzled (FZ), was cloned almost a decade ago because of its role in regulating cell polarity within the plane of an epithelium. In this review, we consider the role of FZ in this intriguing context. We discuss recent progress towards elucidating mechanisms for the intracellular specification of planar polarity, and further review evidence for models of global polarity regulation at the tissue level. The data suggest that a genetic 'cassette', encoding a set of core signaling components, could pattern hair, bristle and ommatidial planar polarity in Drosophila, and that additional tissue-specific factors might explain the diversity of signal responses. Recently described examples from the nematode and frog suggest that the developmental control of cell polarity by FZ receptors might represent a functionally conserved signaling mechanism.