Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning and climbing fiber territory on Purkinje cells.
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is widely expressed in the brain, and plays key roles in various cellular processes in response to both extracellular and intracellular stimuli. Here, we explored the role of FAK in cerebellar development. In the mouse cerebellum, FAK was found to be distributed as tiny cytoplasmic aggregates in various neuronal and glial elements, including Purkinje cells (PCs), Bergmann glia (BG), parallel fiber (PF)-terminals and climbing fiber (CF)-terminals. The neuron/glia-specific ablation of FAK impaired cerebellar foliation, such as variable decreases in foliation sizes and the lack of intercrural and precentral fissures. Some of the BG cells became situated ectopically in the molecular layer. Furthermore, the FAK ablation altered the innervation territories of CFs and PFs on PCs. CF innervation regressed to the basal portion of proximal dendrites and somata, whereas ectopic spines protruded from proximal dendrites and PFs expanded their territory by innervating the ectopic spines. Furthermore, the persistence of surplus CFs innervating PC somata caused multiple innervation. When FAK was selectively ablated in PCs, diminished dendritic innervation and persistent somatic innervation by CFs were observed, whereas cerebellar foliation and cell positioning of BG were normally retained. These results suggest that FAK in various neuronal and glial elements is required for the formation of normal histoarchitecture and cytoarchitecture in the cerebellum, and for the construction of proper innervation territory and synaptic wiring in PCs.
Watanabe
Fumihiro
F
Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan. watamasa@med.hokudai.ac.jp
Miyazaki
Taisuke
T
Takeuchi
Tomonori
T
Fukaya
Masahiro
M
Nomura
Takanori
T
Noguchi
Shigeru
S
Mori
Hisashi
H
Sakimura
Kenji
K
Watanabe
Masahiko
M
Mishina
Masayoshi
M
D000818:Animals; D002531:Cerebellum / Q000201:enzymology* / Q000648:ultrastructure*; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000378:metabolism / Q000648:ultrastructure*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D051416:Focal Adhesion Protein-Tyrosine Kinases