Contributions of VLDLR and LRP8 in the establishment of retinogeniculate projections

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dc.contributorVirginia Techen
dc.contributor.authorSu, Jianminen
dc.contributor.authorKlemm, Michael A.en
dc.contributor.authorJosephson, Anne M.en
dc.contributor.authorFox, Michael A.en
dc.contributor.departmentBiochemistryen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.date.accessed2013-12-06en
dc.date.accessioned2013-12-06T15:56:04Zen
dc.date.available2013-12-06T15:56:04Zen
dc.date.issued2013-06-13en
dc.description.abstractBackground: Retinal ganglion cells (RGCs), the output neurons of the retina, project to over 20 distinct brain nuclei, including the lateral geniculate nucleus (LGN), a thalamic region comprised of three functionally distinct subnuclei: the ventral LGN (vLGN), the dorsal LGN (dLGN) and the intergeniculate leaflet (IGL). We previously identified reelin, an extracellular glycoprotein, as a critical factor that directs class-specific targeting of these subnuclei. Reelin is known to bind to two receptors: very-low-density lipoprotein receptor (VLDLR) and low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2). Here we examined the roles of these canonical reelin receptors in retinogeniculate targeting. Results: To assess the roles of VLDLR and LRP8 in retinogeniculate targeting, we used intraocular injections of fluorescently conjugated cholera toxin B subunit (CTB) to label all RGC axons in vivo. Retinogeniculate projections in mutant mice lacking either VLDLR or LRP8 appeared similar to controls; however, deletion of both receptors resulted in dramatic defects in the pattern of retinal innervation in LGN. Surprisingly, defects in vldlr(-/-); lrp8(-/-) double mutant mice were remarkably different than those observed in mice lacking reelin. First, we failed to observe retinal axons exiting the medial border of the vLGN and IGL to invade distant regions of non-retino-recipient thalamus. Second, an ectopic region of binocular innervation emerged in the dorsomedial pole of vldlr(-/-); lrp8(-/-) mutant dLGN. Analysis of retinal projection development, retinal terminal sizes and LGN cytoarchitecture in vldlr(-/-); lrp8(-/-) mutants, all suggest that a subset of retinal axons destined for the IGL are misrouted to the dorsomedial pole of dLGN in the absence of VLDLR and LRP8. Such mistargeting is likely the result of abnormal migration of IGL neurons into the dorsomedial pole of dLGN in vldlr(-/-); lrp8(-/-) mutants. Conclusions: In contrast to our expectations, the development of both the LGN and retinogeniculate projections appeared dramatically different in mutants lacking either reelin or both canonical reelin receptors. These results suggest that there are reelin-independent functions of VLDLR and LRP8 in LGN development, and VLDLR- and LRP8-independent functions of reelin in class-specific axonal targeting.en
dc.description.sponsorshipNIH EY021222, NS047463en
dc.description.sponsorshipThomas F Jeffress and Kate Miller Jeffress Memorial Trusten
dc.description.sponsorshipVCU Presidential Research Incentive Program (PRIP)en
dc.identifier.citationSu, Jianmin ; Klemm, Michael A. ; Josephson, Anne M. ; et al., Jun 13, 2013. “Contributions of VLDLR and LRP8 in the establishment of retinogeniculate projections,” NEURAL DEVELOPMENT 8(11). DOI: 10.1186/1749-8104-8-11en
dc.identifier.doihttps://doi.org/10.1186/1749-8104-8-11en
dc.identifier.issn1749-8104en
dc.identifier.urihttp://hdl.handle.net/10919/24444en
dc.identifier.urlhttp://www.neuraldevelopment.com/content/pdf/1749-8104-8-11.pdfen
dc.language.isoenen
dc.publisherBioMed Centralen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectReelinen
dc.subjectSynaptic targetingen
dc.subjectIntergeniculate nucleusen
dc.subjectRetinogeniculateen
dc.subjectLateral geniculate nucleusen
dc.subjectAxonen
dc.subjectRetinal terminalen
dc.subjectretinal ganglion-cellsen
dc.subjectvesicular glutamate transportersen
dc.subjectlateral geniculate-nucleusen
dc.subjectneurite outgrowthen
dc.subjectneuronal migrationen
dc.subjectvisual-systemen
dc.subjecttyrosine phosphorylationen
dc.subjectalpha-3-beta-1 integrinen
dc.subjecthippocampal connectionsen
dc.subjectmouse retinaen
dc.subjectDevelopmental Biologyen
dc.subjectNeurosciences & Neurologyen
dc.titleContributions of VLDLR and LRP8 in the establishment of retinogeniculate projectionsen
dc.title.serialNeural Developmenten
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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