The C-elegans F-box/WD-repeat protein LIN-23 functions to limit cell division during development

In multicellular eukaryotes, a complex program of developmental signals reg ulates cell growth and division by controlling the synthesis, activation an d degradation of G(1) cell cycle regulators. Here we describe the lin-23 ge ne of Caenorhabditis elegans, which is required to restrain cell proliferat ion in response to developmental cues. In lin-23 null mutants, all postembr yonic blast cells undergo extra divisions, creating supernumerary cells tha t can differentiate and function normally. In contrast to the inability to regulate the extent of blast cell division in lin-23 mutants, the timing of initial cell cycle entry of blast cells is not affected, lin-23 encodes an F-box/WD-repeat protein that is orthologous to the Saccharomyces cerevisia e gene MET30, the Drosophila melanogaster gene slmb and the human gene beta TRCP, all of which function as components of SCF ubiquitin-ligase complexe s. Lass of function of the Drosophila slmb gene causes the growth of ectopi c appendages in a non-cell autonomous manner, In contrast, lin-23 functions cell autonomously to negatively regulate cell cycle progression, thereby a llowing cell cycle exit in response to developmental signals.