MicroRNA miR-263b-5p Regulates Developmental Growth and Cell Association by Suppressing Laminin A in Drosophila

SIMPLE SUMMARY: The basement membrane (BM) plays a crucial role in various biological processes as a thin layer of the extracellular matrix located at the basal surface of tissues. BMs are regulated by physiological conditions that are altered during development. Specifically, tissue remodeling during metamorphosis in Ecdysozoa is closely associated with BM degradation. However, the mechanisms underlying the regulation of the BM remain unclear. Here, we revealed that the upregulation of the metamorphosis-related microRNA-263b inhibits cell association in the larval fat body by suppressing the expression of Laminin A, which is a major component of the BM. This regulatory mechanism is linked to the developmental growth in Drosophila. Overall, our results provide valuable insights into the regulation of tissue remodeling and growth during metamorphosis. ABSTRACT: Basement membranes (BMs) play important roles under various physiological conditions in animals, including ecdysozoans. During development, BMs undergo alterations through diverse intrinsic and extrinsic regulatory mechanisms; however, the full complement of pathways controlling these changes remain unclear. Here, we found that fat body-overexpression of Drosophila miR-263b, which is highly expressed during the larval-to-pupal transition, resulted in a decrease in the overall size of the larval fat body, and ultimately, in a severe growth defect accompanied by a reduction in cell proliferation and cell size. Interestingly, we further observed that a large proportion of the larval fat body cells were prematurely disassociated from each other. Moreover, we present evidence that miR-263b-5p suppresses the main component of BMs, Laminin A (LanA). Through experiments using RNA interference (RNAi) of LanA, we found that its depletion phenocopied the effects in miR-263b-overexpressing flies. Overall, our findings suggest a potential role for miR-263b in developmental growth and cell association by suppressing LanA expression in the Drosophila fat body.