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.
Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16486-91. doi: 10.1073/pnas.1314819110. Epub 2013 Sep 23.
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.
在发育中的小脑，神经胶质细胞和神经元细胞类型的增殖和分化依赖于 sonic hedgehog（Shh）信号通路的调节。脊椎动物 G 蛋白偶联受体 37 样 1（GPR37L1）基因编码一种假定的 G 蛋白偶联受体，在新生和成年小脑 Bergmann 胶质星形细胞中表达。本研究表明，鼠 Gpr37l1 基因的缺失导致颗粒神经元前体细胞增殖的过早下调和 Bergmann 胶质和浦肯野神经元的早熟成熟。这些改变伴随着成年运动学习和协调能力的提高。Gpr37l1（-/-）小鼠还表现出特定的 Shh 信号级联的修饰。特定的测定表明，在 Bergmann 胶质细胞中，Gpr37l1 与初级纤毛膜相关，并且它与 Shh 主要受体 patched 1 特异性相互作用并共定位。这些发现表明，与 patched 1 相关的 Gpr37l1 受体通过调节 Shh 通路参与调节出生后小脑的发育。
