title: The planar cell polarity protein Vangl2 is required for retinal axon guidance.
abstract: Vangl2 plays a critical role in the establishment of planar cell polarity (PCP). Previously, we detected expression of Vangl2 in the developing retina during late embryogenesis, which led us to investigate the possible role of Vangl2-mediated PCP signaling in eye development. We have generated a Vangl2(BGeo) knock-in mouse allowing us to evaluate Vangl2 mRNA expression during retinal development, and used an isoform-specific antibody to examine Vangl2 protein expression in cryosections. To investigate the role of Vangl2 in retinal development, we examined eyes taken from embryos homozygous for independent alleles of Looptail (Lp, Lp(m1jus) ) mutant mice. We found that Vangl2 mRNA and protein are dynamically expressed in the developing embryonic and postnatal retina, with Vangl2 expression becoming progressively restricted to the ganglion cell layer and optic nerve as the retina matures. The expression pattern of Vangl2 transcript and protein is most prominent in retinal ganglion cells (RGC), and their axons. Additionally, we show that Vangl2 is required for retinal and optic nerve development as Vangl2 (Lp/Lp) mutant embryos display a significantly reduced eye size, marked thickening of the retina, and striking abnormalities in the morphology of the optic nerve (significant hypoplasia, and aberrant exit trajectory). Notably, we identified a salient intraretinal axon guidance defect in Vangl2 (Lp/Lp) mutant embryos through which axon bundles traverse the entire thickness of the retina and become trapped within the subretinal space. Our observations identify a new and essential role for Vangl2-dependent PCP signaling in the intraretinal path-finding of RGC axons.
authors.affiliation: Complex Traits Group, McGill University, Montreal, Canada.|Department of Human Genetics, McGill University, Montreal, Canada.
authors.forename: Vicki
authors.initials: V
authors.lastname: Leung
authors.affiliation: Complex Traits Group, McGill University, Montreal, Canada.|Department of Biochemistry, McGill University, Montreal, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Iliescu
authors.affiliation: Cellular Neurobiology Research Unit, Institut De Recherches Cliniques De Montréal, Montreal, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Jolicoeur
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Gravel
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Canada.
authors.forename: Sergio
authors.initials: S
authors.lastname: Apuzzo
authors.affiliation: Department of Medicine, McGill University Health Center, Montreal, Canada.
authors.forename: Elena
authors.initials: E
authors.lastname: Torban
authors.affiliation: Cellular Neurobiology Research Unit, Institut De Recherches Cliniques De Montréal, Montreal, Canada.|Faculty of Medicine, Université De Montréal, Montreal, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Cayouette
authors.affiliation: Complex Traits Group, McGill University, Montreal, Canada.|Department of Human Genetics, McGill University, Montreal, Canada.|Department of Biochemistry, McGill University, Montreal, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D012160:Retina / Q000166:cytology* / Q000196:embryology; D012165:Retinal Ganglion Cells / Q000166:cytology*
chemical_list: C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins
keywords: Vangl2; axon guidance; planar cell polarity; retinal development; retinal ganglion cells