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    LRP2 Acts as SHH Clearance Receptor to Protect the Retinal Margin from Mitogenic Stimuli (2015)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Christ, Annabel
    Christa, Anna
    Klippert, Julia
    Eule, J Corinna (WE 20)
    Bachmann, Sebastian
    Wallace, Valerie A
    Hammes, Annette
    Willnow, Thomas E
    Quelle
    Developmental cell; 35(1) — S. 36–48
    ISSN: 1878-1551
    Sprache
    Englisch
    Verweise
    DOI: 10.1016/j.devcel.2015.09.001
    Pubmed: 26439398
    Kontakt
    Klinik für kleine Haustiere

    Oertzenweg 19 b
    Haus 1
    14163 Berlin
    +49 30 838 62356
    kleintierklinik@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    During forebrain development, LRP2 promotes morphogen signaling as an auxiliary SHH receptor. However, in the developing retina, LRP2 assumes the opposing function, mediating endocytic clearance of SHH and antagonizing morphogen action. LRP2-mediated clearance prevents spread of SHH activity from the central retina into the retinal margin to protect quiescent progenitor cells in this niche from mitogenic stimuli. Loss of LRP2 in mice increases the sensitivity of the retinal margin for SHH, causing expansion of the retinal progenitor cell pool and hyperproliferation of this tissue. Our findings document the ability of LRP2 to act, in a context-dependent manner, as activator or inhibitor of the SHH pathway. Our current findings uncovered LRP2 activity as the molecular mechanism imposing quiescence of the retinal margin in the mammalian eye and suggest SHH-induced proliferation of the retinal margin as cause of the large eye phenotype observed in mouse models and patients with LRP2 defects.