View Program - 63rd Annual Drosophila Research Conference

Maternal nutrient stores are abundant and transient, providing embryos with energy that fuels development and carbon scaffolds for anabolism. Among this nutrient supply, the fat storage organelles, lipid droplets (LDs), occupy a unique position. At cellularization, most LDs are allocated to the incipient epithelium, while carbohydrate and protein reserves are confined to the yolk cell. Previous work has shown that two distinct mechanisms ensure this privileged localization of LDs. First, the LD protein Jabba keeps LDs and glycogen granules apart; LDs lacking Jabba protein embed into the surface of glycogen granules which results in them being mislocalized to the yolk cell. Second, during the blastoderm stages, LDs move bidirectionally along microtubules, driven by kinesin-1 and cytoplasmic dynein. In the absence of the motor regulator Klar, dynein activity predominates, also resulting in LD mislocalization to the yolk cell. To investigate why this LD distribution exists, we followed Jabba and klar embryos through subsequent embryogenesis and assessed triglyceride consumption, LD localization, and timing of embryogenesis. The yolk cell localized LDs in Jabba and klar persisted through hatching, demonstrating that proper LD localization is crucial to their consumption. This disruption in LD consumption appears to have detrimental consequences for the embryo. On the one hand, knocking down the triglyceride lipase Brummer in Jabba and klar mutants reduces embryo hatching success; under the same conditions, wild type embryos hatch normally. To test whether the hatching delay results from reduced LD consumption or excess LDs damaging the yolk cell, we generated embryos with a reduced maternal supply of LDs using mutants in the LD protein dPLIN2 or in the lipid uptake receptors LpR1 and LpR2. Both genotypes showed significant developmental delays in reciprocal crosses. We therefore conclude embryos respond to reduced access to LD stores with a developmental delay. To elucidate the genetic players in the delay, a candidate RNAi screen was done in Jabba and klar backgrounds. While, in a wild type background, suppression of mTORC1 signaling resulted in reduction in embryo hatching. Surprisingly, this reduction in viability was partially alleviated in Jabba and klar mutants potentially indicating that mTORC1 growth signaling needs to be turned down in a lipid-deprived state. This work demonstrates that organization of LDs in embryos works in concert with metabolism machinery to ensure optimal embryonic development.

Embryonic lipid transport works with TORC1 to ensure rapid and efficient development