Paired-box (pax) and odd-skipped (odd) are two conserved families of developmental transcription factors. We are studying these two transcriptional families in C. elegans, in order to uncover genetic redundancies and functional interactions. In mammals, ODD proteins affect the development of a variety of tissues, including kidney, heart and soft palate, and are implicated in pancreatic and gastric cancer. Mammalian PAX proteins also affect the development of a wide variety of tissues, including palate and kidney. These two transcriptional pathways have been shown to interact in higher animals. Loss of function of Odd genes leads to altered levels of Pax2/8 in frog and mammalian kidneys. Mutation of Pax9 and Odd-skipped related 2 (Osr2) lead to cleft palate in mice, and PAX9 positively affects the expression of OSR2 in that tissue. C. elegans has 5 pax genes, pax-1, pax-2, pax-3, egl-38 and vab-3. Genetic interactions between pax-2 and egl-38 have been previously studied, but not between the remaining family members. Preliminary data shows that RNAi against pax-3 increases lethality in a vab-3(e1062) mutant strain. It has been previously reported that knockdown of either C. elegans odd genes (odd-1 or odd-2) leads to high levels of early larval lethality, due to defects in intestinal development. In our hands, an odd-1(tm848) mutant that deletes most of the gene or enhanced RNAi against odd-1 do not result in high-level larval lethality. Fluorescent reporters of each odd gene (generous gift of the Rothman lab) show expression in adult posterior intestinal nuclei, with the brightest expression of ODD-1::GFP in Int9R. ODD-2 additionally shows strong expression in what appears to be the three rectal gland cells. RNAi against odd-1 reduced the expression of ODD-2::GFP in the posterior intestinal cells, but not the rectal gland cells. Studies have been initiated to identify interactions between odd and pax in C. elegans. RNAi against the pax gene, vab-3, in an ODD-1::GFP strain resulted in variable brightness and number of GFP-expressing intestinal nuclei. This variability is consistent with a previous finding of a variable transgene expression phenotype found by RNAi against vab-3. RNAi against pax-1 led to a slight deformity in the posterior intestine. Three pax genes have putative ODD binding sites in their promoters; experiments are planned to study the effect of odd mutants/RNAi on the expression of these genes.