Document Type

Article

Publication Date

8-25-1998

Publication Title

Development (Cambridge, England)

Department

Department of Biological Sciences

Abstract

C. elegans cki-1 encodes a member of the CIP/KIP family of cyclin-dependent kinase inhibitors, and functions to link postembryonic developmental programs to cell cycle progression. The expression pattern of cki-1::GFP suggests that cki-1 is developmentally regulated in blast cells coincident with G1, and in differentiating cells. Ectopic expression of CKI-1 can prematurely arrest cells in G1, while reducing cki-1 activity by RNA-mediated interference (RNAi) causes extra larval cell divisions, suggesting a role for cki-1 in the developmental control of

INTRODUCTION

The proper development of a multicellular organism requires the precise orchestration of cell proliferation and differentiation. Despite considerable progress toward understanding the mechanisms of cell cycle progression in single cells, less is known about the coordination of the cell cycle with development in a multicellular context. Developmental control of cell cycle is likely implemented by signals acting on limiting components of the cell cycle machinery (Edgar and Lehner, 1996). For example, in Drosophila, the timing and number of embryonic cell cycles is controlled by the developmental regulation of Cyclin E, String (cdc25), and E2F, which are limiting cell cycle activators (Duronio and O’Farrell, 1994, 1995; Knoblich et al., 1994; Duronio et al., 1995; Richardson et al., 1995; Sauer et al., 1995; Lehner and Lane, 1997), and by the activity of Dacapo, the Drosophila member of the CIP/KIP family of cyclin-dependent kinase inhibitors (CKIs) (de Nooij et al., 1996; Lane et al., 1996). Cells at the anterior side of the morphogenetic furrow in the fly eye imaginal disc are synchronized in G1 of their penultimate cell cycle by roughex and rca1, which regulate cyclin A (Thomas et al., 1994; Dong et al., 1997). In C. elegans, the number of cell divisions in diverse cell lineages is limited by the activity of cul-1, which likely acts by regulating the degradation of G1 cyclins (Kipreos et al., 1996; Mathias et al., 1996).

CKIs block cell division by inhibiting cyclin-dependent kinase activity necessary for the G1/S transition (Harper and Elledge, 1996) and hence these proteins are potential mediators

G1/S. cki-1 activity is required for the suspension of cell cycling that occurs in dauer larvae and starved L1 larvae in response to environmental signals. In vulva precursor cells (VPCs), a pathway of heterochronic genes acts via cki- 1 to maintain VPCs in G1 during the L2 stage.

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