A fatty acid anabolic pathway in specialized-cells sustains a remote signal that controls egg activation in Drosophila.

Egg activation, representing the critical oocyte-to-embryo transition, provokes meiosis completion, modification of the vitelline membrane to prevent polyspermy, and translation of maternally provided mRNAs. This transition is triggered by a calcium signal induced by spermatozoon fertilization in most animal species, but not in insects. In Drosophila melanogaster, mature oocytes remain arrested at metaphase-I of meiosis and the calcium-dependent activation occurs while the oocyte moves through the genital tract. Here, we discovered that the oenocytes of fruitfly females are required for egg activation. Oenocytes, cells specialized in lipid-metabolism, are located beneath the abdominal cuticle. In adult flies, they synthesize the fatty acids (FAs) that are the precursors of cuticular hydrocarbons (CHCs), including pheromones. The oenocyte-targeted knockdown of a set of FA-anabolic enzymes, involved in very-long-chain fatty acid (VLCFA) synthesis, leads to a defect in egg activation. Given that some but not all of the identified enzymes are required for CHC/pheromone biogenesis, this putative VLCFA-dependent remote control may rely on an as-yet unidentified CHC or may function in parallel to CHC biogenesis. Additionally, we discovered that the most posterior ventral oenocyte cluster is in close proximity to the uterus. Since oocytes dissected from females deficient in this FA-anabolic pathway can be activated in vitro, this regulatory loop likely operates upstream of the calcium trigger. To our knowledge, our findings provide the first evidence that a physiological extra-genital signal remotely controls egg activation. Moreover, our study highlights a potential metabolic link between pheromone-mediated partner recognition and egg activation. Author summary: Efficient sexual reproduction requires gamete formation and maturation, partner mating, fecundation and the triggering of embryonic development. Deciphering the underlying physiological regulatory processes represents a major scientific challenge, crucial both for medical issues and agricultural pest control. A pivotal step in the reproductive process, known as egg activation, is the oocyte-to-embryo transition. In a wide range of metazoan species, this activation is provoked by the entry of the spermatozoon into the oocyte. Conversely, in insects, egg activation is initiated as the oocyte moves through the female genital tract, operating independently of spermatozoon entry. Here, we discovered that egg activation in Drosophila depends on a set of anabolic enzymes required for very-long-chain fatty acid (VLCFA) synthesis in the oenocytes. The oenocytes, abdominal cells specialized in lipid metabolism, are necessary for the biogenesis of cuticular hydrocarbons and pheromones. To our knowledge, our findings provide the first evidence that a non-genital physiological signal remotely governs egg activation. Given that pheromone-deficient Drosophila females attract males regardless of their species, we propose that pheromone biogenesis and this VLCFA-dependent remote signal might have co-evolved to prevent the development of hybrid individuals. [ABSTRACT FROM AUTHOR]