title: Lrp5/6 are required for cerebellar development and for suppressing TH expression in Purkinje cells via β-catenin.
abstract: BACKGROUND
  The cerebellum is responsible for coordinating motor functions and has a unique laminated architecture. Purkinje cells are inhibitory neurons and represent the only output from the cerebellar cortex. Tyrosine hydroxylase (TH) is the key enzyme for the synthesis of catecholamines, including dopamine and noradrenaline, and it is normally not expressed in cerebellar neurons.
  
  
  RESULTS
  We report here that the low-density lipoprotein receptors (Lrp) 5 and 6, Wnt co-receptors, are required for the development of the cerebellum and for suppressing ectopic TH expression in Purkinje cells. Simultaneous inactivation of Lrp 5 and 6 by Nestin-Cre results in defective lamination and foliation of the cerebellum during postnatal development. Surprisingly, TH is ectopically expressed by Purkinje cells, although they still keep its other neurochemical characteristics. These phenotypes are also observed in the cerebellum of GFAP-Cre;β-catenin(flox/flox) mice, and AAV2-Cre-mediated gene deletion leads to ectopic TH expression in Purkinje cells of β-catenin(flox/flox) mice as well.
  
  
  CONCLUSIONS
  Our results revealed a new role of the canonical Lrp5/6-β-catenin pathway in regulating the morphogenesis of the cerebellum during postnatal development.
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.|Department of Anatomy and Neurobiology, Collaborative Innovation Centerfor Brain Science, Tongji University School of Medicine, Shanghai, 200092, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.|Department of Anatomy and Neurobiology, Collaborative Innovation Centerfor Brain Science, Tongji University School of Medicine, Shanghai, 200092, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.|Department of Anatomy and Neurobiology, Collaborative Innovation Centerfor Brain Science, Tongji University School of Medicine, Shanghai, 200092, China.
authors.forename: Ning-Ning
authors.initials: NN
authors.lastname: Song
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.|Department of Anatomy and Neurobiology, Collaborative Innovation Centerfor Brain Science, Tongji University School of Medicine, Shanghai, 200092, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.|Department of Anatomy and Neurobiology, Collaborative Innovation Centerfor Brain Science, Tongji University School of Medicine, Shanghai, 200092, China.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Sun
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.|Department of Anatomy and Neurobiology, Collaborative Innovation Centerfor Brain Science, Tongji University School of Medicine, Shanghai, 200092, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Hu
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.|Department of Anatomy and Neurobiology, Collaborative Innovation Centerfor Brain Science, Tongji University School of Medicine, Shanghai, 200092, China.
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.|Clinical and Translational Research Center, East Hospital, Shanghai, 200120, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Prevention, Tongji University School of Medicine, Shanghai, 200092, China. jueli@tongji.edu.cn.
authors.forename: Jue
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. dingyuqiang@vip.163.com.|Department of Anatomy and Neurobiology, Collaborative Innovation Centerfor Brain Science, Tongji University School of Medicine, Shanghai, 200092, China. dingyuqiang@vip.163.com.
authors.forename: Yu-Qiang
authors.initials: YQ
authors.lastname: Ding
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002395:Catecholamines / Q000378:metabolism; D002454:Cell Differentiation; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D000229:Dependovirus / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000378:metabolism*; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000378:metabolism*; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D011689:Purkinje Cells / Q000201:enzymology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555483:Lrp5 protein, mouse; C555476:Lrp6 protein, mouse; D051176:beta Catenin; D014446:Tyrosine 3-Monooxygenase; C045073:Cre recombinase; D019426:Integrases