MUTATIONS AFFECTING DEVELOPMENT OF ZEBRAFISH DIGESTIVE ORGANS

The zebrafish gastrointestinal system matures in a manner akin to high er vertebrates, We describe nine mutations that perturb development of these organs. Normally, by the fourth day postfertilization the diges tive organs are formed, the epithelial cells of the intestine are pola rized and express digestive enzymes, the hepatocytes secrete bile, and the pancreatic islets and acini generate immunoreactive insulin and c arboxypeptidase A, respectively. Seven mutations cause arrest of intes tinal epithelial development after formation of the tube but before ce ll polarization is completed, These perturb different regions of the i ntestine. Six preferentially affect foregut, and one the hindgut, In o ne of the foregut mutations the esophagus does not form, Two mutations cause hepatic degeneration, The pancreas is affected in four mutants, all of which also perturb anterior intestine, The pancreatic exocrine cells are selectively affected in these four mutations, Exocrine prec ursor cells appear, as identified by GATA-5 expression, but do not dif ferentiate and acini do not form, The pancreatic islets are spared, an d endocrine cells mature and synthesize insulin, These gastrointestina l mutations may be informative with regard to patterning and crucial l ineage decisions during organogenesis, and may be relevant to diabetes , congenital dysmorphogenesis and disorders of cell proliferation.