Since its release in 2000, WormBase (http://www.wormbase.org) has grown from a small resource focusing on a single species and serving a dedicated research community, to one now spanning 15 species essential to the broader biomedical and agricultural research fields. To enhance the rate of curation, we have automated the identification of key data in the scientific literature and use similar methodology for data extraction. To ease access to the data, we are collaborating with journals to link entities in research publications to their report pages at WormBase. To facilitate discovery, we have added new views of the data, integrated large-scale datasets and expanded descriptions of models for human disease. Finally, we have introduced a dramatic overhaul of the WormBase website for public beta testing. Designed to balance complexity and usability, the new site is species-agnostic, highly customizable, and interactive. Casual users and developers alike will be able to leverage the public RESTful application programming interface (API) to generate custom data mining solutions and extensions to the site. We report on the growth of our database and on our work in keeping pace with the growing demand for data, efforts to anticipate the requirements of users and new collaborations with the larger science community.

Fibroblast growth factor (FGF) signaling controls a vast array of biological processes including cell differentiation and migration, wound healing and malignancy. In vertebrates, FGF signaling is complex, with over 100 predicted FGF ligand-receptor combinations. Drosophila melanogaster presents a simpler model system in which to study FGF signaling, with only three ligands and two FGF receptors (FGFRs) identified. Here we analyze the specificity of FGFR [Heartless (Htl) and Breathless (Btl)]activation by each of the FGF ligands [Pyramus (Pyr), Thisbe (Ths) and Branchless (Bnl)] in Drosophila. We confirm that both Pyr and Ths can activate Htl, and that only Bnl can activate Btl. To examine the role of each ligand in supporting activation of the Htl FGFR, we utilize genetic approaches that focus on the earliest stages of embryonic development. When pyrand ths are equivalently expressed using the Gal4 system, these ligands support qualitatively different FGFR signaling responses. Both Pyr and Ths function in a non-autonomous fashion to support mesoderm spreading during gastrulation, but Pyr exhibits a longer functional range. pyr and ths single mutants exhibit defects in mesoderm spreading during gastrulation, yet only pyr mutants exhibit severe defects in dorsal mesoderm specification. We demonstrate that the Drosophila FGFs have different activities and that cell migration and differentiation have different ligand requirements. Furthermore, these FGF ligands are not regulated solely by differential expression, but the sequences of these linked genes have evolved to serve different functions. We contend that inherent properties of FGF ligands make them suitable to support specific FGF-dependent processes, and that FGF ligands are not always interchangeable.

SUMMARYCaudal visceral mesoderm (CVM) cells migrate synchronously towards the anterior of the Drosophila embryo as two distinct groups located on each side of the body, in order to specify longitudinal muscles that ensheath the gut. Little is known about the molecular cues that guide cells along this path, the longest migration of embryogenesis, except that they closely associate with trunk visceral mesoderm (TVM). The expression of the fibroblast growth factor receptor (FGFR) heartless and its ligands, pyramus (pyr) and thisbe (ths), within CVM and TVM cells, respectively, suggested FGF signaling may influence CVM cell guidance. In FGF mutants, CVM cells die before reaching the anterior region of the TVM. However, an earlier phenotype observed was that the two cell clusters lose direction and converge at the midline. Live in vivo imaging and tracking analyses identified that the movements of CVM cells were slower and no longer synchronous. Moreover, CVM cells were found to cross over from one group to the other, disrupting bilateral symmetry, whereas such mixing was never observed in wild-type embryos. Ectopic expression of either Pyr or Ths was sufficient to redirect CVM cell movement, but only when the endogenous source of these ligands was absent. Collectively, our results show that FGF signaling regulates directional movement of CVM cells and that native presentation of both FGF ligands together is most effective at attracting cells. This study also has general implications, as it suggests that the activity supported by two FGF ligands in concert differs from their activities in isolation.