Fig. 5. Genetic and molecular models for LIN-46 activity in developmental timing. (A) Genetic models for the heterochronic pathway governing fate choices at two stages. (Left) Interactions governing the L2/L3 fate choice. The circled regulators x and y have not been identified and may in fact represent multiple factors. lin-14 is depicted in its role in the L2/L3 fate decision only (lin-14B activity). The position of daf-12 is based on previous studies (Antebi et al., 1998; Seggerson et al., 2002); its role does not appear to be analogous to that of lin-46. (Right) Interactions governing the L/A switch. The effect of lin-28 or lin-46 on let-7 expression or activity has not been determined, and may be indirect. The linear pathway from let-7 to adult fates is based on previous studies (Abrahante et al., 2003; Lin et al., 2003). (B) A molecular model for LIN-46 protein function. LIN-46 may scaffold a multiprotein assembly constituting a developmental timing complex that regulates the expression of downstream heterochronic genes and promotes L3- and adult-specific cell fates. Broken arrow indicates that the effects of the complex may be either positive or negative, and either direct or indirect. LIN-28 may act as a negative regulator of one or more components of that complex, probably at the level of gene expression.