cki-1 and
cki-2 are adjacent genes that encode C. elegans members of the mammalian
p21 Cip1 /p27 Kip1 family of cyclin-dependent kinase inhibitors (CKIs) (1, 2). Hong et al. (2) showed that RNAi of
cki-1 , but not
cki-2 , causes extra cell divisions in a number of larval cell lineages. We found that embryos homozygous for a deficiency deleting both genes show hyperplasia in many lineages, elongation defects, and excess cell corpses. A cosmid containing the cki genes can apparently rescue these phenotypes, suggesting that the cki genes are required for timely exit from the embryonic cell cycle, morphogenesis and suppression of programmed cell death (PCD). However, the rescued deficiency embryos contain fewer nuclei than wild type, perhaps indicating that overexpression of the cki gene(s) from the cosmid causes precocious cell-cycle arrest or that a positive cell cycle regulator is deleted by the deficiency. Previous studies using GFP reporter constructs suggested that
cki-1 is expressed when embryonic and post-embryonic cells become post-mitotic. Surprisingly,
cki-2 is ubiquitously expressed in proliferating embryonic cells as well as in post-mitotic cells (1, 2). Although CKIs have been found in proliferating cells in other animals, the significance of this expression has yet to be established. Despite the embryonic expression of the cki genes in many cells, previous RNAi experiments failed to show an embryonic phenotype for either cki gene alone or in combination. However, we recently found that RNAi directed against an extended region of
cki-2 causes a phenotype reminiscent of that of the deficiency, perhaps indicating that
cki-2 per se is critical for embryonic cell-cycle exit. We are currently attempting to generate knockouts of the cki genes and are characterizing the early embryonic expression of the CKI proteins in an effort to elucidate their roles in cell proliferation, cell-cycle exit, and PCD during embryogenesis. 1. Gendreau, S.B. and Rothman, J.H. (1997). 11th International Worm Meeting. 2. Hong, Y., Roy, R. and Ambros, V. (1998). Development 125, 3585-3597.