title: Ectopic cerebellar cell migration causes maldevelopment of Purkinje cells and abnormal motor behaviour in Cxcr4 null mice.
abstract: SDF-1/CXCR4 signalling plays an important role in neuronal cell migration and brain development. However, the impact of CXCR4 deficiency in the postnatal mouse brain is still poorly understood. Here, we demonstrate the importance of CXCR4 on cerebellar development and motor behaviour by conditional inactivation of Cxcr4 in the central nervous system. We found CXCR4 plays a key role in cerebellar development. Its loss leads to defects in Purkinje cell dentritogenesis and axonal projection in vivo but not in cell culture. Transcriptome analysis revealed the most significantly affected pathways in the Cxcr4 deficient developing cerebellum are involved in extra cellular matrix receptor interactions and focal adhesion. Consistent with functional impairment of the cerebellum, Cxcr4 knockout mice have poor coordination and balance performance in skilled motor tests. Together, these results suggest ectopic the migration of granule cells impairs development of Purkinje cells, causes gross cerebellar anatomical disruption and leads to behavioural motor defects in Cxcr4 null mice.
authors: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan ; Healthy Aging Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors: Guo-Jen
authors: GJ
authors: Huang
authors: The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: Andrew
authors: A
authors: Edwards
authors: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors: Cheng-Yu
authors: CY
authors: Tsai
authors: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors: Yi-Shin
authors: YS
authors: Lee
authors: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors: Lei
authors: L
authors: Peng
authors: Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors: Takumi
authors: T
authors: Era
authors: Laboratory for Molecular Membrane Neuroscience, Brain Science Institute, RIKEN, Wako, Saitama, Japan.
authors: Yoshio
authors: Y
authors: Hirabayashi
authors: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors: Ching-Yen
authors: CY
authors: Tsai
authors: Center for Developmental Biology, RIKEN, Kobe, Japan.
authors: Shin-Ichi
authors: S
authors: Nishikawa
authors: Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors: Yoichiro
authors: Y
authors: Iwakura
authors: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors: Shu-Jen
authors: SJ
authors: Chen
authors: The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: Jonathan
authors: J
authors: Flint
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: C514936:CXCR4 protein, mouse; D019718:Receptors, CXCR4