Progression through mitosis requires activation of the anaphase promoting complex (APC), which triggers ubiquitin-dependent degradation of specific proteins such as mitotic cyclins. Recent studies have shown that two related WD40 repeat proteins, CDC20/Fizzy and HCT1/Fizzy-related, might be substrate-specific activators of APC. The C. elegans genome sequencing project has identified a C. elegans homolog of fizzy-related (fzr) , which we named
fzr-1 . To understand the role of
fzr-1 in the course of development, we have isolated a deletion allele of
fzr-1 by the PCR-oriented screen.
fzr-1 homozyogotes showed variable phenotypes: 64% of them were arrested at L1-L2, 14% arrested at L3-L4, and the rest (12%) became sterile adults. In the sterile worms, gonad arms were hardly elongated, and no differentiation of uterus and spermathecae was observed. In these unelongated gonads, germ cells appeared to undergo proliferation to some extent, but they failed to complete gametogenesis, producing no mature oocytes. Most
fzr-1 sterile adults were associated with the Unc phenotype, suggesting a defect in ventral-cord motor neurons. Missing vulvae and protruded vulvae were also often observed. The apparent defects in somatic gonad, germ cells, ventral-cord neurons and vulva suggest that
fzr-1 is required for postembryonic lineage in various tissues. Similar Stu (Sterile and Uncordinated) phenotype has been observed in general cell cycle mutants, such as
lin-5 ,
lin-6 and stu mutants, supproting the model that
fzr-1 is involved in cell cycle regulation. Notably, whereas loss of fzr function in Drosophila results in an extra cycle of cell division in the epidermis, the
fzr-1 defect in C. elegans appears to cause premature arrest of cell division. Developmental stage-specific Northern analysis revealed that expression of
fzr-1 is most abundant in embryo, gradually decreases toward L4, and then increases again in the adult stage. The high expression observed in adults is likely to correspond to its expression in oocytes and fertilized embryos. The mRNA level of
fzr-1 apparently correlates with the cell cycle activities at each stage, again supporting its involvement in cell cycle regulation.