Chemical genetics in zebrafish

With their small size and external development, zebrafish embryos are highly amenable to small molecule screening.  Moreover, it is possible to take advantage of transgenic lines to identify small molecules that may specifically affect a particular tissue type.  We have begun to apply small molecule screening to identify compounds that selectively block blood vessel or lymphatic vessel formation, or those that affect circulatory function.  By taking advantage of the Small Molecule Screening facility here at UMass Med and access to high-throughput imaging, we have successfully identified compounds that preferentially block lymphatic or blood vessel growth.  Identifying the targets of these molecules will allow novel insights into vascular or lymphatic development.  At the same time, they may serve as important lead molecules for therapeutic applications.