PgmNr W4013: TGFβ and prostaglandin synthesis in C. elegans: linking environmental cues to sperm motility function.

Authors:
Muhan Hu; Michael Miller


Institutes
University of Alabama at Birmingham, Birmingham, AL.


Keyword: Gametogenesis, Fertilization, Egg-embryo transition

Abstract:

Sexual reproduction is critical for maintaining population diversity and species survival. Environmental exposures are thought to influence animal fertility, but the underlying mechanisms are not well understood. Fertilization depends on sperm guidance mechanisms for locating maturing oocytes within the oviduct. The signaling pathways that mediate sperm guidance have been well studied in marine species, but less is known in internally fertilizing animals, such as C. elegans. We have shown that C. elegans oocytes synthesize specific classes of F-series prostaglandins (PGFs) that guide migrating sperm toward them. These PGFs are synthesized via an unknown and possibly evolutionarily conserved metabolic pathway. The DAF-7 TGFβ homologue acts in ASI sensory neurons, downstream of ascaroside pheromones, to modulate oocyte PGF synthesis, linking environmental perception to sperm performance. Loss of the DAF-1 type I TGFβ receptor causes sperm guidance defects and decreased PGF synthesis. Here we show that the PGF synthesis phenotype can be suppressed by daf-3 co-SMAD loss. DAF-3 activity is required in part within the germ line, suggesting DAF-3 transcriptional targets in oocyte precursors modulate PGF metabolism. To identify these TGFβ targets, we conducted RNA sequencing analyses of wild type, daf-1 mutant, and daf-1;daf-3 mutant hermaphrodites. Currently, RNAi screens are being used to test whether the TGFβ target (direct or indirect) genes play roles in PGF metabolism. Genome-editing strategies are ongoing to investigate how TGFβ signals are transduced to the germ line. Mass spectrometry approaches are being developed to help identify biochemical steps mediated by TGFβ. These efforts are providing insight into the molecular mechanisms of fertilization and the link between environmental factors and sperm function.



Wormbase Genetic Index
1. daf-7
2. daf-1
3. daf-3