The investigations of the Fishman laboratory are directed at understanding vertebrate morphogenesis. Genetics and embryology are used in combination to dissect organogenesis, especially of the cardiovasculature, gastrointestinal and hematopoietic systems.

Previous work has not utilized genetics in a systematic fashion to approach development of the heart or, for that matter, any organ system. The cornerstone of this project is the zebrafish, Danio rerio, which develops a functioning heart and vasculature within two days. We have identified a cardiogenic region of the blastula, and found unexpectedly early separation of progenitors for different chambers. Cell tracking and transplantation are being used to elucidate the embryological relationships between the myocardium, endocardium, vessels, and blood cells, and genes are being cloned which are useful in characterizing or perturbing these lineages. Cardiovascular mutants have been generated by several approaches, including radiation and ENU, the latter in collaboration with Wolfgang Driever. We have found that recessive cardiovascular mutations are reasonably frequent and can perturb unitary decisions, evidenced by discrete effects upon the heart and vasculature. For example, some mutants lack all heart valves, or are missing the entire endocardium, or maintain bilateral hearts. Other mutations provide models of human disease, such as porphyria, arrhythmias, electromechanical dissociation, and aortic coarctation. These mutants are under evaluation with regard to the underlying cell biology, their degree of cell autonomy, and for the mapping and cloning of the relevant genes. Similar types of mutational analyses are underway with regard to the gastrointestinal tract, pancreas, and liver.