DEVELOPMENTAL EFFECT OF POLYAMINE DEPLETION IN CAENORHABDITIS-ELEGANS

Ornithine decarboxylase (ODC) catalyses the conversion of ornithine to putrescine, an obligate precursor to the polyamines spermidine and sp ermine. We reported previously that homozygous odc-1 (pc13) worms have no detectable ODC activity. Despite their inability to make polyamine s, these mutant worms appear normal, but with a slight reduction in to tal brood size, when grown in complex medium that presumably contains polyamines. We now show that when ODC-deficient worms are transferred to polyamine-free medium, they show a strong phenotype. odc-1 worms ha ve two different fates, depending upon the developmental stage at whic h polyamines are removed. If the polyamines are removed at the L1 larv al stage, the mutant animals develop into adult hermaphrodites that pr oduce very few or no eggs. In contrast, if mutant larvae at the later L4 stage of development are transferred to polyamine-deficient medium, they develop and lay eggs normally. However, approx. 90% of the eggs yield embryos that, although well differentiated, arrest at early stag e 3. Either maternal or zygotic expression of ODC provides partial res cue of embryonic lethality. Supplementing deficient medium with the po lyamine spermidine allows ODC-deficient worms to develop as on complex medium. Together, these findings suggest that ODC activity is most cr itically required during oogenesis and embryogenesis and, furthermore, that exogenous polyamines can override the requirement for ODC activi ty.