DUAL ROLE FOR THE ZESTE-WHITE3 SHAGGY-ENCODED KINASE IN MESODERM AND HEART DEVELOPMENT OF DROSOPHILA/

A Drosophila homolog of the serine/ threonine kinase GSK-3 beta, encod ed by the zest-white3/ shaggy gene (zw3), has been implicated as a mat ernally provided antagonist of zygotic signaling by the secreted segme ntation gene wingless (wg). The wg signal apparently causes a spatiall y localized inhibition of the ubiquitous repressor function of zw3. Th is double negative mechanism of signal transduction has been shown to mediate the patterning Function of Wg in a number of developmental pro cesses. Although wg is absolutely required for specifying the heart pr ogenitors within the mesoderm of Drosophila, the role of zw3 in this p rocess has been unclear. Here, we present evidence that zw3 has a dual role in mesoderm develop ment: (1) zw3 acts as an antagonist in cardi ogenic wg signal transduction, and (2) zw3 also seems to be required t o promote positively the formation of a larger mesodermal region, the tinman- and dpp-dependent ''dorsal mesoderm,'' which is a prerequisite not only for cardiogenesis, but also for visceral mesoderm formation. We also demonstrate that a recently identified proximal component of the wg cascade, which is a transcription factor encoded by pangolin/dT CF (dTCF), also seems to mediate wg-dependent cardiogenesis. Further, we present evidence that Notch (N), which opposes wg signaling in othe r situations, is unlikely to be directly involved in the cardiogenic w g pathway, but seems to have multiple other myogenic functions, one of which is to inhibit mesoderm differentiation altogether, when overexp ressed as a constitutively active form. (C) 1998 Wiley Liss, Inc.