title: The Reelin receptors Apoer2 and Vldlr coordinate the patterning of Purkinje cell topography in the developing mouse cerebellum.
abstract: The adult cerebellar cortex is comprised of reproducible arrays of transverse zones and parasagittal stripes of Purkinje cells. Adult stripes are created through the perinatal rostrocaudal dispersion of embryonic Purkinje cell clusters, triggered by signaling through the Reelin pathway. Reelin is secreted by neurons in the external granular layer and deep cerebellar nuclei and binds to two high affinity extracellular receptors on Purkinje cells-the Very low density lipoprotein receptor (Vldlr) and apolipoprotein E receptor 2 (Apoer2). In mice null for either Reelin or double null for Vldlr and Apoer2, Purkinje cell clusters fail to disperse. Here we report that animals null for either Vldlr or Apoer2 individually, exhibit specific and parasagittally-restricted Purkinje cell ectopias. For example, in mice lacking Apoer2 function immunostaining reveals ectopic Purkinje cells that are largely restricted to the zebrin II-immunonegative population of the anterior vermis. In contrast, mice null for Vldlr have a much larger population of ectopic Purkinje cells that includes members from both the zebrin II-immunonegative and -immunopositive phenotypes. HSP25 immunoreactivity reveals that in Vldlr null animals a large portion of zebrin II-immunopositive ectopic cells are probably destined to become stripes in the central zone (lobules VI-VII). A small population of ectopic zebrin II-immunonegative Purkinje cells is also observed in animals heterozygous for both receptors (Apoer2(+/-): Vldlr(+/-)), but no ectopia is present in mice heterozygous for either receptor alone. These results indicate that Apoer2 and Vldlr coordinate the dispersal of distinct, but overlapping subsets of Purkinje cells in the developing cerebellum.
authors.affiliation: Genes and Development Research Group and Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, Faculty of Medicine, The University of Calgary, Calgary, Alberta, Canada.
authors.forename: Matt
authors.initials: M
authors.lastname: Larouche
authors.forename: Uwe
authors.initials: U
authors.lastname: Beffert
authors.forename: Joachim
authors.initials: J
authors.lastname: Herz
authors.forename: Richard
authors.initials: R
authors.lastname: Hawkes
mesh_terms: D000818:Animals; D019521:Body Patterning; D002531:Cerebellum / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D004627:Embryonic Induction; D005838:Genotype; D026502:LDL-Receptor Related Proteins; D051379:Mice; D011689:Purkinje Cells / Q000166:cytology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology*; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000502:physiology*; D000091042:Reelin Protein
chemical_list: D026502:LDL-Receptor Related Proteins; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C469363:reelin receptor; C000717128:Reln protein, mouse