Oocyte meiotic maturation is a conserved developmental transition, defects in which are the major cause of human birth defects and infertility. C. elegans provides a genetic model for studying the control of oocyte meiotic maturation by hormonal signaling and soma-germline interactions. The meiotic maturation processes in C. elegans and mammals share a number of similarities. Major sperm protein (MSP) and luteinizing hormone, though unrelated in sequence, both trigger meiotic resumption using somatic Gas-adenylate cyclase pathways and soma-germline gap-junctional communication. Shared responses include cortical cytoskeletal rearrangement, nuclear envelope breakdown, meiotic spindle assembly, and changes important for the oocyte-to-embryo transition. Here we describe progress in elucidating the genetic mechanisms by which the somatic gonad receives the MSP signal and transduces the oocyte response. Gas-adenylate cyclase signaling in the follicle-like gonadal sheath cells is required for all described MSP responses in the germline. Because the gonadal sheath cells form gap junctions with oocytes, we considered whether cAMP generated in sheath cells might trigger cAMP-dependent protein kinase A (PKA) activation in the oocyte. We used genetic mosaic analysis to test this possibility. We found that kin-1, which encodes the PKA catalytic subunit, is required for meiotic maturation in the sheath cells, but not oocytes. To identify downstream effectors of MSP signaling, we conducted a genetic screen for mutations that suppress the sterility caused by a null mutation in the adenylate cyclase (acy-4) required in sheath cells for meiotic maturation. We recovered 63 suppressor of adenylate cyclase (sacy) mutations. We are in the process of mapping and cloning sacy mutations using whole genome sequencing. Preliminary analysis of sacy mutations has identified components of the CoREST repressor complex and a DEAD-box RNA helicase. Genetic mosaic analysis of kin-1 in an spr-5 mutant background indicates that spr-5 is epistatic. Therefore, spr-5, which encodes the LSD1 histone demethylase component of the CoREST complex, might participate in setting the germline context by repressing the transcription of genes that interfere with the normal signaling mechanism. Three allelic sacy mutations appear to result from missense mutations in a highly conserved DEAD-box helicase. Interestingly, this helicase was biochemically characterized as a component of OMA-1 ribonucleoprotein particles (see a poster by C. Spike). These data provide insight into how germline context and translational control ensure that meiotic maturation is coupled to sperm availability.

Affiliation:
- GCD, University of Minnesota, Minneapolis, MN USA