The CIP/KIP family of Cyclin-dependent Kinase Inhibitors (CKIs) function to arrest the cell cycle at the appropriate time during metazoan development. In C. elegans, two apparent CIP/KIP CKIs are encoded by the adjacent
cki-1 and
cki-2 genes (1). We previously reported that deficiencies that remove both cki genes cause extra embryonic cell divisions in multiple tissues and accumulation of excess cell corpses, and that a cosmid containing these genes can rescue these deficiency phenotypes (2). We recently found that the
cki-1 transgene alone can rescue the hyperplastic phenotype of homozygous deficiency embryos, while the
cki-2 transgene shows only very weak rescuing activity, suggesting that
cki-1 is essential for embryonic cell cycle arrest. In support of this hypothesis,
cki-1(RNAi) but not
cki-2(RNAi) leads to embryonic hyperplasia in most tissues and the appearance of many cell corpses. Interestingly, embryonic germ cells arrest the cell cycle in a CKI-1-independent manner. The CIP/KIP CKIs in vertebrates have been implicated in terminal differentiation as well as exit from the cell cycle. We previously demonstrated that
cki-1(RNAi) causes loss of a differentiation marker in the adult somatic gonad (3). We recently found that
cki-1(RNAi) can eliminate expression of two late differentiation markers during embryogenesis, one in seam cells and one in the gut, suggesting that
cki-1 is required to promote terminal stages of differentiation. We are currently attempting to determine (1) which stage in differentiation is blocked by loss of
cki-1 activity, (2) whether terminal differentiation in the other lineages requires
cki-1 activity, and (3) whether CKI-1 promotes differentiation through a cyclin-dependent kinase activity. 1. Hong, Y et al. (1998). Development 125, 3585-3597. Feng, H et al. (1999). Nature Cell. Biol. 1, 486-492. 2. Gendreau, SB and Rothman, JH. (1997). 11th International Worm Meeting. 3. Fukuyama, M et al (1998). 1998 West Coast Worm Meeting.