ZEBRA FISH MYC FAMILY AND MAX GENES - DIFFERENTIAL EXPRESSION AND ONCOGENIC ACTIVITY THROUGHOUT VERTEBRATE EVOLUTION

To gain insight into the role of Myc family oncoproteins and their ass ociated protein Max in vertebrate growth and development, we sought to identify homologs in the zebra fish (Brachydanio rerio). A combinatio n of a polymerase chain reaction-based cloning strategy and low-string ency hybridization screening allowed for the isolation of zebra fish c -, N-, and L-myc and max genes; subsequent structural characterization showed a high degree of conservation in regions that encode motifs of known functional significance. On the functional level, zebra fish Ma x, like its mammalian counterpart, served to suppress the transformati on activity of mouse c-Myc in rat embryo fibroblasts. In addition, the zebra fish c-myc gene proved capable of cooperating with an activated H-ras to effect the malignant transformation of mammalian cells, albe it with diminished potency compared with mouse c-myc. With respect to their roles in normal developing tissues, the differential temporal an d spatial patterns of steady-state mRNA expression observed for each z ebra fish myc family member suggest unique functions for L-myc in earl y embryogenesis, for N-myc in establishment and growth of early organ systems, and for c-myc in increasingly differentiated tissues. Further more, significant alterations in the steady-state expression of zebra fish myc family genes concomitant with relatively constant mar express ion support the emerging model of regulation of Myc function in cellul ar growth and differentiation.