FBF-1 and FBF-2 Regulate the Size of the Mitotic Region in the C. elegans Germline

Abstract

In the C. elegans germline, GLP-1/Notch signaling and two nearly identical RNA binding proteins, FBF-1 and FBF-2, promote proliferation. Here, we show that the fbf-1 and fbf-2 genes are largely redundant for promoting mitosis but that they have opposite roles in fine-tuning the size of the mitotic region. The mitotic region is smaller than normal in fbf-1 mutants but larger than normal in fbf-2 mutants. Consistent with gene-specific roles, fbf-2 expression is limited to the distal germline, while fbf-1 expression is broader. The fbf-2 gene, but apparently not fbf-1, is controlled by GLP-1/Notch signaling, and the abundance of FBF-1 and FBF-2 proteins is limited by reciprocal 3'UTR repression. We propose that the divergent fbf genes and their regulatory subnetwork enable a precise control over size of the mitotic region. Therefore, fbf-1 and fbf-2 provide a paradigm for how recently duplicated genes can diverge to fine-tune patterning during animal development.

Caenorhabditis elegans germ line: A model for stem cell biology

“…D: "The intensity function from the large data set with 95% confidence intervals (dashed lines) for the wild-type (blue) plus the selected glp-1(ar202) mutants (red)." E: "The wild-type intensity profile from D overlaid with the approximate steady-state protein concentration levels estimated from previous publications (Crittenden et al, 1994;Jones et al, 1996;Hansen et al, 2004b;Lamont et al, 2004). For GLP-1, we depict the region of high penetrance of high-level cell membrane-associated protein only; significant levels of internal GLP-1 are present in the germ line proximal to CD 12 (see Crittenden et al, 1994, Figs.…”

“…The data support a general model whereby the outcome of the activated GLP-1 pathway interferes with the accumulation of GLD-1 protein thereby preventing meiotic entry in the distal part of the zone (Hansen et al 2004b). The pumilio-related proteins FBF-1 and FBF-2 are required redundantly for late larval and adult maintenance of the proliferative zone and mediate the effect of the GLP-1 pathway on GLD-1-dependent meiotic entry (Crittenden et al, 2002;Lamont et al, 2004). The two fbf genes encode very similar proteins and have redundant functions, but they also have some distinct effects on germline pattern.…”

“…They appear to negatively regulate each other. LAG-1 binding sites are present in the fbf-2 upstream region, suggesting a direct role for FBF-2 in mediating GLP-1 activity (Crittenden et al, 2002;Lamont et al, 2004). Genetic evidence suggests that at least one additional pathway is required to prevent meiotic entry in response to GLP-1 (Hansen et al, 2004a).…”

“…The steady-state levels of several proteins known to affect the position of the proliferative zone border are nonuniform across the proliferative zone, including GLP-1, FBF-1, FBF-2, and GLD-1 (Hansen et al, 2004b;Lamont et al, 2004;Crittenden et al, 2006;Fig. 5).…”

“…How, exactly, the measurable steady-state levels of GLP-1 correlates to activity of the receptor is not yet known. In the DTC-associated subzone, relatively high FBF-2 protein levels are observed, while the level of FBF-1 protein is lower relative to cells further proximal (Lamont et al, 2004). Further studies are needed to understand fully the significance of these protein expression patterns with respect to germ cell behavior.…”