We examined the role of angiogenesis and the need for receptor signaling using chemical inhibition of the vascular endothelial growth factor receptor in the adult zebrafish tail fin. Using a smallmolecule inhibitor, we were able to exert precise control over blood vessel regeneration. An angiogenic limit to tissue regeneration was determined, as avascular tissue containing skin, pigment, neuronal axons and bone precursors could regenerate up to about 1 mm. This indicates that tissues can regenerate without direct interaction with endothelial cells and at a distance from blood supply. We also investigated whether the effects of chemical inhibition could be enhanced in zebrafish vascular mutants. We found that adult zebrafish, heterozygous for a mutation in the critical receptor effector phospholipase Cγ1, show a greater sensitivity to chemical inhibition. This study illustrates the utility of the adult zebrafish as a new model system for receptor signaling and chemical biology.In the postgenomic era, assigning gene function and delineating signaling pathways require the combined effort of multiple disciplines and approaches. The use of chemical probes has immense potential in examining biological processes and developing specific therapeutic compounds. On the biological side, these goals can be achieved through the appropriate use of model systems. In vitro and cell-based assays have been widely used for drug discovery and chemical library screening 1-3 . Whole organism approaches are also possible using yeast, worms, flies or zebrafish embryos 4,5 . Of these, the zebrafish, as a vertebrate organism, has reasonable counterparts to many mammalian organs, tissues and cell types. As such, it affords an opportunity to investigate more complex biological processes 5 . The transparency of the zebrafish embryo has facilitated visual scoring of phenotypic defects. Thus, it has been used extensively for developmental biology and genetics, and in the last few years as a new model Correspondence should be addressed to J.C. (joanne.chan@childrens.harvard.edu).. 6 These authors contributed equally to this work. COMPETING INTERESTS STATEMENT The authors declare competing financial interests (see the Nature Chemical Biology website for details).Note: Supplementary information is available on the Nature Chemical Biology website. NIH Public Access Author ManuscriptNat Chem Biol. Author manuscript; available in PMC 2006 August 9. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript for chemical biology 4,5 . However, tissue growth and differentiation are very different in an embryo versus in an adult animal. Embryonic development involves precise coordination of genetic programs that allow the building of a whole organism from a single cell. Therefore, chemical genetic analysis in embryos is dictated by the timing of developmental events. In an adult animal, organ maintenance and cellular needs are different, with turnover and repair being important. Another crucial consideration in developing therape...

Genetic analyses in zebrafish identify a novel physical signaling mechanism that drives formation of invadopodia-like structures and promotes cell invasion in vivo.

Smooth muscle cells provide structural support for many tissues and control essential physiological processes, such as blood pressure and gastrointestinal motility. Relatively little is known about early stages of intestinal smooth muscle development and its relationship to the development of the enteric nervous system, which regulates intestinal motility. Here, we report an evolutionarily conserved 523 base pair regulatory element within the promoter of the zebrafish sm22α-b (transgelin1) gene that directs transgene expression in smooth muscle cells of the intestine and other tissues. Comparative genomic analysis identified a conserved motif within this element consisting of two Serum Response Factor binding sites that is also present in the promoters of many mammalian smooth muscle genes. We established a stable line expressing GFP in smooth muscle cell and used this line to describe lineage relationships among cells within different intestinal smooth muscle layers and their co-development with the enteric nervous system (ENS).

Adherens junction remodeling allows changes in cell shape and position. Zilberman et al. show through live imaging that CDC-42 is dispensable for epithelial cell polarization, but its RhoGAP-regulated activity is needed to control junctional actin organization during embryo elongation.