Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor

• Published in: Proceedings of the National Academy of Sciences - PNAS 2013-10, Vol.110 (41), p.16486-16491
• Main Authors: Marazziti, Daniela, Di Pietro, Chiara, Golini, Elisabetta, Mandillo, Silvia, La Sala, Gina, Matteoni, Rafaele, Tocchini-Valentini, Glauco P.
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes; Biological Sciences; Blotting, Western; Cell Proliferation; Cerebellum; Cerebellum - cytology; Cerebellum - growth & development; Developmental biology; DNA Primers - genetics; Fluorescent Antibody Technique; Gene Deletion; Gene expression; Genetic Vectors - genetics; Genotypes; Glycoproteins; Hedgehog Proteins - metabolism; Immunoprecipitation; In Situ Hybridization; Male animals; Mice; Mice, Knockout; Mitogens - metabolism; Motor ability; Neuroglia; Neuroglia - physiology; Neurons; Patched Receptors; Patched-1 Receptor; Psychomotor Performance - physiology; Purkinje cells; Purkinje Cells - physiology; Receptors; Receptors, Cell Surface - metabolism; Receptors, G-Protein-Coupled - genetics; Rodents; Signal transduction; T cell receptors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1314819110

In the developing cerebellum, the proliferation and differentiation of glial and neuronal cell types depend on the modulation of the sonic hedgehog (Shh) signaling pathway. The vertebrate G-protein-coupled receptor 37-like 1 (GPR37L1) gene encodes a putative G-protein–coupled receptor that is expressed in newborn and adult cerebellar Bergmann glia astrocytes. This study shows that the ablation of the murine Gpr37l1 gene results in premature down-regulation of proliferation of granule neuron precursors and precocious maturation of Bergmann glia and Purkinje neurons. These alterations are accompanied by improved adult motor learning and coordination. Gpr37l1 ⁻/⁻ mice also exhibit specific modifications of the Shh signaling cascade. Specific assays show that in Bergmann glia cells Gpr37l1 is associated with primary cilium membranes and it specifically interacts and colocalizes with the Shh primary receptor, patched 1. These findings indicate that the patched 1–associated Gpr37l1 receptor participates in the regulation of postnatal cerebellum development by modulating the Shh pathway.