Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor.
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.
Consiglio Nazionale delle Ricerche, European Mouse Mutant Archive-Infrafrontier-International Mouse Phenotyping Consortium, Istituto di Biologia Cellulare e Neurobiologia, I-00015 Monterotondo Scalo (Rome), Italy.
Daniela
D
Marazziti
Chiara
C
Di Pietro
Elisabetta
E
Golini
Silvia
S
Mandillo
Gina
G
La Sala
Rafaele
R
Matteoni
Glauco P
GP
Tocchini-Valentini
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development*; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D005822:Genetic Vectors / Q000235:genetics; D053823:Hedgehog Proteins / Q000378:metabolism; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008934:Mitogens / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011597:Psychomotor Performance / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
D017931:DNA Primers; C509804:Gpr37 protein, mouse; D053823:Hedgehog Proteins; D008934:Mitogens; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled
mitogenic signaling; mutant mouse model