The Myc oncoprotein is implicated in over 100,000 American cancer deaths annually; therefore, understanding the biology of Myc and Myc-like proteins is essential for understanding the mechanisms of Myc-dependent transformation. The existence of multiple Myc family members and regulatory networks complicate analysis in higher eukaryotes. C. elegans has a simplified Myc network with single representatives of the Mad (
mdl-1), Max (
mxl-1), and Mlx (
mxl-2) families. The nearest relative to Myc in C. elegans is Myc and Mondo-
like-1 (
mml-1), which has sequence features of both Myc and the Myc analog, MondoA. Similar to MondoA, MML-1 and MXL-2 dimerize, and this heterodimer activates transcription from E-box (CACGTG)-dependent reporters. To understand the in vivo function of
mml-1, we are characterizing the
mml-1(
ok849) allele. This allele has an in frame deletion of 401aa, which removes the DNA binding domain, yet produces a stable truncated protein product. Therefore, even though a stable product is produced, it is unlikely to bind DNA and activate transcription from its target genes. As MML-1 and Myc are highly similar, it is surprising that
mml-1(
ok849) worms appear wildtype in all aspects examined. To uncover phenotypes, we conducted an RNAi screen against genes previously implicated in some aspect of Myc or Mondo function. RNAi against
bar-1, a -catenin ortholog, causes a ruptured (Rup) phenotype in N2 worms that is suppressed in the
mml-1(
ok849) background. To examine this finding further, we crossed the
mml-1(
ok849) allele with worms carrying a
bar-1 null mutation. We observe that the mildly penetrant protruding vulva defect caused by
bar-1(-) is converted into a highly penetrant Rup phenotype in double mutant worms. Cell fate analysis showed that the cell fate specification defects in P5.p and P7.p caused by the
bar-1(-) allele are partially suppressed in
mml-1(
ok849);
bar-1(-) worms. We observe that the expression patterns of MML-1 and BAR-1 are mutually exclusive, i.e., MML-1 is expressed in Hyp7, while BAR-1 is expressed in seam cells and P3.p-P8.p. Current experiments are designed to understand this reciprocal expression pattern, and the relative contribution of MML-1 to vulval cell fate specification. Finally, experiments focusing on
mml-1(
ok849) males suggest that these worms harbor a defect in mating behavior resulting in decreased mating and a decreased number of males per brood. Current experiments are focusing on elucidating the mechanism of this phenotype.