The increased use of simpler metazoans with smaller genomes has, in recent years, played an increasingly important role in defining and dissecting a number of processes and key players of particular importance to biology. Already these are impacting on our understanding of liver development and Panobinostat order disease. The opportunities presented by the study of simpler organisms to dissect function and pathology are now growing. The use of nonvertebrate and lower vertebrate models provides researchers with a number of key advantages. These include

defined and relatively limited genomes, a short lifespan, ease of genetic manipulation, in some examples direct visualization of an organ or tissue, and of course homologous biological systems with higher vertebrates. Additionally, for these lower organisms, antisense or knockout strategies are easily deployed to dissect out multiple components of pathways of interest for pathological processes. Effectively, libraries of knockout or knockdown organisms can be created for the research community. For example, in the last few years, critical observations relating to liver biology and development have been driven selleck screening library by the zebrafish model. This includes the identification of the Wnt2b gene as critical for normal fish liver specification and development.3 Looking to the future, however, fish offer multicellular/multiorgan models for screening. Because the zebrafish embryo

is transparent and has relatively close homology with other higher vertebrates, it renders itself as an extraordinary yet simple multiorgan in vivo MCE model in which to screen drugs.4, 5 Fish can be created that incorporate reporter systems expressing

fluorescent protein when a target gene is transcribed. Multiwell plates in which each well contains a single transparent fish embryo can be exposed to novel therapies, and compounds regulating transcription in particular pathways may be rapidly identified. This opens the door to, for example, screening existing licensed drugs for novel indications. Additionally, because the array can take place in a 96-well plate format, literally thousands of compounds can be screened in a whole vertebrate organism in vivo assay. It is easy to see how organisms such as zebrafish, which possess a defined liver, might be used as models for hepatological research. It is less clear, though, for Drosophila (the fruit fly), which lacks a discrete organ homolog for the liver. Traditionally, the fat body, the major glycogen store in the fly, oriented in a segmental fashion during larval development, has been seen as being the equivalent of the liver for the fruit fly. However, current evidence suggests that Drosophila does not have a discrete organ ortholog to the liver, but rather that specific metabolic functions associated with the mammalian liver have evolved to be delivered by different tissues.