Insulin and germline proliferation in Caenorhabditis elegans

Abstract

Germline proliferation in Caenorhabditis elegans is emerging as a compelling model system for understanding the molecular basis for the developmental and physiological control of cell proliferation. This review covers the discovery and implications of the role of the insulin/IGF-like signaling pathway in germline proliferation during germline development. This pathway plays a host of important roles in C. elegans biology. Its role in germline proliferation is important to generate the proper adult stem/progenitor population and to ensure optimal fecundity. Moreover, in this role, it is restricted to reproductive (as opposed to dauer) larval stages and impinges on the G2 of the cell cycle. Two putative insulin ligands are especially important for the germline role but do not mediate signaling in other tissues. A picture is emerging of a complex web of developmentally and temporally restricted, ligand- and tissue-specific responses to insulin signaling. Avenues for future studies include the regulation of specific insulin-like ligands and the mechanisms for tissue-specific responses to them.

Figure 3.1

Cartoon depictions of L3 and early L4 stage C. elegans hermaphrodites. Bilobed gonad is indicated with proliferative germ cells in light gray, meiotic cells dark gray to black. Crescent-shaped nuclei characteristic of the transition zone are depicted. White central portion indicates position of future spermathecae and uterine cells. Distal tip cells are shown in red and distal and proximal sheath cells in lighter and darker blue, respectively.

Figure 3.2

Latent niche concept and related screening strategy. See text for details.

Figure 3.3

Insulin/IGF signaling pathways in C. elegans and mammals. Corresponding proteins or classes of proteins are indicated. Broad black line indicates the cell membrane and thin line indicates the nuclear membrane.

Figure 3.4

Influence of DAF-2 activity on the proliferative zone. Top: number of nuclei in the proliferative zone in gonad arms of animals of the indicated ages in wildtype and in a daf-2 mutant under two temperature conditions, continuous growth at 20 °C or a shift from 15 to 25 °C. Bottom: images of distal germline nuclei of young adult wild-type and daf-2 mutants. Positions of the proliferative and transition zones are indicated. Asterisk marks the distal end in all panels. Scale bar indicates 20 µm. Figure modified from (Michaelson et al., 2010).

Figure 3.5

Experimental strategy to test dependence of sheath cell-ablation phenotype on daf-16 activity. Left: unablated conditions. Right: ablation conditions. See text for details. Bottom: Sheath cells and distal tip cell are marked with GFP. Scale bar indicates 20 µm. Modified from Michaelson et al. (2010).

Figure 3.6

Model for the control of larval germline proliferation in response to GLP-1/Notch, DAF-2/IIR, and distal sheath signals.