C. elegans hermaphrodite germ line. (A) A dissected N2 (wild-type) hermaphrodite gonad immunostained with anti-REC-8 antibodies (green) for proliferative germ cells, anti-HIM-3 antibodies (red) for differentiating germ cells, and DAPI (blue) for DNA. The transition zone marks the region where meiotic entry is first visible. The somatic distal tip cell (DTC) caps the very distal end (asterisk) of the gonad. Scale bar: 50 µm. (B,C) GLP-1/Notch signalling inhibits the activities of GLD-1 NOS-3 and GLD-2 GLD-3, which allows proteins necessary for proliferation and proliferative fate-promoting proteins to be active. More proximally, GLP-1/Notch signalling levels decrease, and GLD-1 NOS-3 and GLD-2 GLD-3 become active, downregulating the activities of proteins necessary for proliferation and proteins promoting the proliferative fate. The proteasome acts in parallel to further decrease the activity of GLP-1/Notch signalling, proliferative fate-promoting proteins, and proteins necessary for proliferation. (D) The E3 ligase provides a scaffold to bind the E2 ubiquitin conjugating enzyme (E2) and substrate recognition subunit (SRS) to form a multi-subunit complex that binds the substrate. (E) The monomeric E3 ligase includes the SRS function, thus binding both the substrate and the E2 conjugating enzyme. (F) A living worm with ozIs2[GLD-1::GFP] observed under a dissecting microscope, showing the regions of GLD-1::GFP expression. (G) Diagram illustrating the increase in the space between the GLD-1::GFP expression in ozIs2[GLD-1::GFP] animals that have a larger proliferative (mitotic) zone (middle) as compared with wild-type animals (top) and tumorous animals (bottom).