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Abstract
Lipin is evolutionarily conserved from yeast to mammals. Although its roles in lipid metabolism in adipocyte tissue, skeletal muscle, and the liver, and as a transcriptional co-activator are known, its functions during development are still under investigation. In this study, we analyzed the role of Drosophila lipin (dLipin) in development. Specifically, we showed that the tissue-selective knockdown of dLipin in the wing pouch led to an atrophied wing. Elevated DNA damage was observed in the wing imaginal disc of dLipin-knockdown flies. dLipin dysfunction induced accumulation of cells in S phase and significantly reduced the number of mitotic cells, indicating DNA damage-induced activation of the G2/M checkpoint. Reduced expression of cyclin B, which is critical for the G2 to M transition, was observed in the margin of the wing imaginal disc of dLipin-knockdown flies. The knockdown of dLipin led to increased apoptotic cell death in the wing imaginal disc. Thus, our results suggest that dLipin is involved in DNA replication during normal cell cycle progression in wing development of Drosophila melanogaster.
Highlights
The phospholipid components of biological membranes are pivotal for cellular processes including growth, differentiation, and transport, as phospholipids participate in important signaling cascades [1,2,3]
We found that Drosophila lipin (dLipin) signals are detected throughout the wing imaginal discs with relatively stronger signals in the anterior part of the margin and notum, and slightly lesser signals in the wing pouch and hinge (Figure 1a)
We suggest that dLipin is necessary for the cell cycle progression subsequent to normal DNA replication during wing development of D. melanogaster
Summary
The phospholipid components of biological membranes are pivotal for cellular processes including growth, differentiation, and transport, as phospholipids participate in important signaling cascades [1,2,3]. Phospholipid synthesis involves phosphatidic acid (PA) and diacylglycerol (DAG), both of which have critical roles in signaling cascades, energy storage, and lipid anabolism pathways [4]. In Drosophila, decreased expression of Drosophila lipin (dLipin) was found to affect the normal development of the fat body, which is the major tissue for TAG storage in invertebrates [23], and resulted in down-regulation of the insulin-receptor-controlled PI3K-Akt pathway and increased hemolymph sugar levels [24]. In mammals, blocking TORC1 dephosphorylates lipin 1, leading to its translocation from the cytoplasm into the nucleus, where it affects nuclear protein levels, but not mRNA levels, of the transcription factor sterol regulatory element-binding protein 1 (SREBP1), which is a main regulator of genes that are related to the biosynthesis of fatty acid, cholesterol, TAG, and phospholipid [25]
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