Beets, Isabel, Van Rompay, Liesbeth, Caers, Jelle, Borghgraef, Charline, Schoofs, Liliane, Temmerman, Liesbet
[
International Worm Meeting,
2015]
Vitellogenesis, the process by which maternal yolk is formed, is thought to be a critical step in reproduction of all egg-laying animals. In vertebrates, the well-characterized hormonal hypothalamus-pituitary-gonad regulatory system drives reproductive success, including yolk protein synthesis by the liver, in a time- and sex-dependent manner. Whether similar control mechanisms exist for invertebrate reproduction, is an open question in surprisingly unexplored scientific territory. It can be expected that genetic control of reproduction in invertebrates will to a certain extent be similar to the vertebrate system, conform genome sequencing data, whereas many invertebrate-, clade- or species-specific factors are thought to exist as well - e.g. depending on distinct reproductive cycles. Therefore, we reasoned intestinal yolk protein production to be a suitable downstream readout to unravel the nematode reproductive axis in more detail. Using a GFP-tagged yolk protein as a reporter, we performed a forward genetic screen in C. elegans, focusing on mutants overtly defective in yolk protein production. Via a combined mapping and whole-genome sequencing strategy we identified five mutant alleles, corresponding to three novel regulatory genes involved in C. elegans vitellogenesis. We further confirmed that indeed, mutations in genes encoding a vitellogenin regulating Caenorhabditis-specific, C. elegans homeobox and low-density lipoprotein receptor related protein disrupt yolk protein synthesis at the transcriptional and translational level. Our data on each of these molecular players support the view that parallel pathways, some of which contain evolutionarily unique regulators, exert control over vitellogenesis in C. elegans. As opposed to general assumptions, we show that a virtually absent yolk protein pool does not necessarily imply a severely affected reproductive potential. This raises questions on the relevance and quantitative needs of yolk for reproduction. Further research, e.g. concerning the consistency of the yolk-depleted eggs and other reproduction-related defects, will be important to further raise our understanding of invertebrate control of reproduction.