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Development (Cambridge, England)


Department of Biological Sciences


In Caenorhabditis elegans, the fates of the six multipotent vulva precursor cells (VPCs) are specified by extracellular signals. One VPC expresses the primary (1°) fate in response to a Ras-mediated inductive signal from the gonad. The two VPCs flanking the 1° cell each express secondary (2°) fates in response to lin-12-mediated lateral signaling. The remaining three VPCs each adopt the non- vulval tertiary (3°) fate. Here I describe experiments examining how the selection of these vulval fates is affected by cell cycle arrest and cell cycle-restricted lin-12 activity. The results suggest that lin-12 participates in two


Cell-cell signaling is a common mode of cell fate specification in animal development. In many cases, signals must act at defined developmental stages or steps in a cell lineage, so a cell’s ability to select a specific fate in response to particular extracellular signals can be influenced by timing mechanisms linked to developmental stage (Servetnick and Grainger, 1991; Slack, 1991) or the cell cycle (Gomer and Firtel, 1987; McConnell and Kaznowski, 1991; Thomas et al., 1994; Weigmann and Lehner, 1995). Temporal or cell cycle control of developmental decisions may be particularly important in situations where a cell is sensitive to multiple signals that specify distinct outcomes and specific cell fate choices need to be executed with a certain priority or temporal sequence.

Situations where developmental events are linked to cell cycle progression have been identified by the ability of cell cycle inhibitors to prevent the expression of molecular or phenotypic developmental markers, as is the case for a dependence of even- skipped expression on completion of S phase in the Drosophila nervous system (Weigmann and Lehner, 1995). In other situations, developmental decisions, and even overt differentiation, can occur independently of cell cycle progression, for example, in the case of neural development in Xenopus (Harris and Hartenstein, 1991). In such cases, the relative timing of events may still be critical to normal development, but are linked to temporal cues other than cell cycle progression.

Vulva development in Caenorhabditis elegans offers a convenient experimental system for exploring the temporal and

developmental decisions separable by cell cycle phase: lin- 12 must act prior to the end of VPC S phase to influence a 1° versus 2° cell fate choice, but must act after VPC S phase to influence a 3° versus 2° cell fate choice. Coupling developmental decisions to cell cycle transitions may provide a mechanism for prioritizing or ordering choices of cell fates for multipotential cells.


V. Ambros

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