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The C. elegans Intestine As a Model for Intercellular Lumen Morphogenesis and In Vivo Polarized Membrane Biogenesis at the Single-cell Level: Labeling by Antibody Staining, RNAi Loss-of-function Analysis and Imaging
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MESD is essential for apical localization of megalin/LRP2 in the visceral endoderm

Janet K Lighthouse, Liqun Zhang, Jen-Chih Hsieh

    Developmental Dynamics : an Official Publication of the American Association of Anatomists
    |February 22, 2011
    PubMed

    Insights

    Mesoderm Ectoderm Development gene (Mesd) acts as a chaperone for low-density lipoprotein receptor (LRP) proteins, crucial for Wnt signaling and receptor maturation. Loss of Mesd causes developmental defects due to impaired Wnt signaling and endocytic functions.

    Area of Science:

    • Developmental Biology
    • Molecular Biology
    • Genetics

    Background:

    • Mesoderm Ectoderm Development gene (Mesd) is a known chaperone for Wnt co-receptors low-density lipoprotein receptor-related protein (LRP) 5 and 6 (LRP5/6).
    • Mesd-deficient embryos exhibit polarity defects and impaired gastrulation, suggesting a broader role beyond Wnt signaling.

    Purpose of the Study:

    • To investigate the role of MESD in the maturation of the broader low-density lipoprotein receptor (LRP) family.
    • To elucidate the mechanisms underlying the developmental defects in Mesd-deficient embryos.

    Main Methods:

    • Generation of a targeted Mesd knockout mouse model.
    • In vitro assays to assess MESD's role in LRP maturation.
    • Analysis of Wnt signaling pathways, pluripotency markers (Oct4, Nanog, Sox2), and LRP2 (Megalin/MEG) localization in Mesd mutants.

    Main Results:

    • Loss of Mesd blocks Wnt signaling in vivo and impairs LRP maturation.
    • Mesd deficiency leads to the persistence of pluripotency markers, indicating a block in epiblast differentiation.
    • MESD is essential for apical localization of LRP2 (Megalin/MEG), causing impaired endocytic function.

    Conclusions:

    • MESD functions as a general chaperone for multiple LRP receptors, not just LRP5/6.
    • The Mesd phenotype arises from both impaired Wnt signaling and defective endocytosis due to misfolded LRPs.
    • This study highlights MESD's critical role in embryonic development through LRP maturation and function.

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