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LRP2 acts as SHH clearance receptor to protect the retinal margin from mitogenic stimuli

Item Type:Article
Title:LRP2 acts as SHH clearance receptor to protect the retinal margin from mitogenic stimuli
Creators Name:Christ, A. and Christa, A. and Klippert, J. and Eule, J.C. and Bachmann, S. and Wallace, V.A. and Hammes, A. and Willnow, T.E.
Abstract: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.
Keywords:Cell Proliferation, Developmental Gene Expression Regulation, Hedgehog Proteins, Hydrophthalmos, Immunoenzyme Techniques, In Situ Hybridization, Inbred C57BL Mice, Knockout Mice, Low Density Lipoprotein Receptor-Related Protein-2, Mammalian Embryo, Mitogens, Neurons, Retina, Signal Transduction, Stem Cells, Animals, Mice
Source:Developmental Cell
Publisher:Cell Press / Elsevier
Page Range:36-48
Date:12 October 2015
Official Publication:https://doi.org/10.1016/j.devcel.2015.09.001
PubMed:View item in PubMed

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