In animals, oocyte development arrests at the first meiotic prophase. Oocyte maturation then resumes in response to specific triggers, which, in C. elegans, take the form of the major sperm protein (MSP, an ephrin signalling antagonist). Now, two studies by David Greenstein and co-workers shed light on how MSP triggers oocyte maturation, and identify crucial roles for Notch signalling and Gαs-adenylate cyclase (GαAC) in both oocyte growth and maturation.
In their first study (see p. 2211), these researchers report that all germline MSP-dependent oocyte meiotic maturation events require GαAC signalling in the somatic sheath cells of the gonad, but not in the germ cells themselves. They demonstrate that the MSP-mediated events that occur in the germline, including MPK-1 MAP kinase activation, which triggers meiotic maturation, and cortical microtubule reorganisation, which probably promotes meiotic spindle assembly, depend on GαAC signalling. Gap junctions appear to function downstream of GαAC signalling, as mutations in gap junction protein-encoding genes suppress GαAC-associated defects. GαAC signalling also promotes MSP-dependent oocyte growth and cytoplasmic streaming.
In their second study (on p. 2223), these investigators go on to show that GLP-1/Notch signalling in the somatic distal tip cells (DTCs) regulates MSP-dependent oocyte growth and cytoplasmic streaming. Mutations in glp-1 lead to large oocytes, and, by using genetic mosaic analysis, in which the fates of clonally derived cells that are genetically distinct from the surrounding tissue are traced, the authors show that germline glp-1 regulates normal oocyte growth. The DTC-expressed GLP-1 ligands LAG-2 and APX-1 probably mediate this regulation, as DTC ablation or LAG-2 and APX-1 co-depletion result in enlarged oocytes. Moreover, glp-1 mutations lead to higher rates of cytoplasmic streaming and to delayed oocyte cellularisation, as long as certain gap junction proteins and core apoptotic pathways are functional. These results indicate that GLP-1/Notch signalling restricts oocytes to their normal size in the presence of MSP signalling.
Taken together, these findings suggest that two major signalling centres in the adult C. elegans hermaphrodite gonad - GLP-1/Notch distally and MSP proximally - function in opposition to regulate meiotic maturation and oocyte growth, a regulatory interaction that might be conserved in other species.