MicroRNA miR-252-5p regulates the Notch signaling pathway by targeting Rab6 in Drosophila wing development

Do Hwan Lim, Min Seok Choi, Ji Won Jeon, Young Sik Lee

    Research output: Contribution to journalArticlepeer-review

    6 Citations (Scopus)

    Abstract

    The Notch signaling pathway plays a central role in the development of various organisms. However, dysregulation of microRNAs (miRNAs), which are crucial regulators of gene expression, can disrupt signaling pathways at all stages of development. Although Notch signaling is involved in wing development in Drosophila, the mechanism underlying miRNA-based regulation of the Notch signaling pathway is unclear. Here, we report that loss of Drosophila miR-252 increases the size of adult wings, whereas the overexpression of miR-252 in specific compartments of larval wing discs leads to patterning defects in the adult wings. The miR-252 overexpression-induced wing phenotypes were caused by aberrant Notch signaling with intracellular accumulation of the full-length Notch receptor during development, which could be due to defects in intracellular Notch trafficking associated with its recycling to the plasma membrane and autophagy-mediated degradation. Moreover, we identified Rab6 as a direct target of miR-252-5p; Rab6 encodes a small Ras-like GTPase that regulates endosomal trafficking pathways. Consistent with this finding, RNAi-mediated downregulation of Rab6 led to similar defects in both wing patterning and Notch signaling. Notably, co-overexpression of Rab6 completely rescued the wing phenotype associated with miR-252 overexpression, further supporting that Rab6 is a biologically relevant target of miR-252-5p in the context of wing development. Thus, our data indicate that the miR-252-5p-Rab6 regulatory axis is involved in Drosophila wing development by controlling the Notch signaling pathway.

    Original languageEnglish
    Pages (from-to)1431-1444
    Number of pages14
    JournalInsect Science
    Volume30
    Issue number5
    DOIs
    Publication statusPublished - 2023 Oct

    Bibliographical note

    Funding Information:
    We thank the Bloomington Stock Center and the Developmental Studies Hybridoma Bank (DSHB) for providing us with fly strains and antibodies, respectively. We also thank T. Neufeld and K. Köhler for providing a fly strain and an antibody, respectively. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIT) (2021R1F1A1059864 to D‐H.L. and 2021R1A2C1006353 to Y.S.L.) and a Korea University Grant (to Y.S.L.). Drosophila

    Funding Information:
    We thank the Bloomington Drosophila Stock Center and the Developmental Studies Hybridoma Bank (DSHB) for providing us with fly strains and antibodies, respectively. We also thank T. Neufeld and K. Köhler for providing a fly strain and an antibody, respectively. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIT) (2021R1F1A1059864 to D-H.L. and 2021R1A2C1006353 to Y.S.L.) and a Korea University Grant (to Y.S.L.).

    Publisher Copyright:
    © 2023 Institute of Zoology, Chinese Academy of Sciences.

    Keywords

    • Drosophila
    • Notch signaling
    • Rab6
    • miR-252-5p
    • wing development

    ASJC Scopus subject areas

    • Ecology, Evolution, Behavior and Systematics
    • Agronomy and Crop Science
    • General Biochemistry,Genetics and Molecular Biology
    • Insect Science

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