The establishment of anterior-posterior polarity occurs rapidly, and is tightly coordinated with meiosis and eggshell formation. The precise timing of the process requires that many of the macromolecules involved must be synthesized and in the correct location prior to fertilization. Lipids play a vital role during the oocyte-to-embryo transition. A precise lipid balance must be maintained to support signaling prior to fertilization as well as membrane structural integrity and eggshell formation after. Here, we demonstrate that MEL-3, the C. elegans homolog to mammalian holocarboxylase synthetase, is an essential player in lipid biosynthesis and in the events following fertilization of the embryo.
We found that reduction of MEL-3 function disrupts anterior-posterior polarity and permeability barrier formation in the C. elegans embryo similarly to loss of de novo fatty acid synthesis. We confirmed MEL-3’s crucial role in de novo fatty acid synthesis using stable isotope labeling. Further, by genetically manipulating the bacterial food source of C. elegans to limit the dietary fatty acid precursors available to worms, we show that MEL-3 function is essential for larval development when dietary malonyl-CoA is limited.
Importantly, we can rescue larval development in mel-3 mutants with supplemental biotin; however, we cannot rescue embryonic phenotypes with biotin or fatty acids. The observation that the mutants can utilize exogenous biotin suggests that they retain some enzymatic function and that the worm can use dietary metabolites to sustain post-embryonic development even when MEL-3 function is reduced, but full function is essential for the embryo. This suggests that the worm diet cannot compensate for either the rapid rate of lipid synthesis required at the transition, or for the specific lipid products produced. We conclude that C. elegans has a specific requirement for fully functioning lipid biosynthesis machinery during the oocyte-to-embryo transition. .
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