Developmental effect of polyamine depletion in Caenorhabditis elegans

Abstract

Ornithine decarboxylase (ODC) catalyses the conversion of ornithine to putrescine, an obligate precursor to the polyamines spermidine and spermine. We reported previously that homozygous odc-1 (pc13) worms have no detectable ODC activity. Despite their inability to make polyamines, these mutant worms appear normal, but with a slight reduction in total 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 have two different fates, depending upon the developmental stage at which polyamines are removed. If the polyamines are removed at the L1 larval stage, the mutant animals develop into adult hermaphrodites that produce 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 stage 3. Either maternal or zygotic expression of ODC provides partial rescue of embryonic lethality. Supplementing deficient medium with the polyamine spermidine allows ODC-deficient worms to develop as on complex medium. Together, these findings suggest that ODC activity is most critically required during oogenesis and embryogenesis and, furthermore, that exogenous polyamines can override the requirement for ODC activity.