title: Loss of the neuron-specific F-box protein FBXO41 models an ataxia-like phenotype in mice with neuronal migration defects and degeneration in the cerebellum.
abstract: The cerebellum is crucial for sensorimotor coordination. The cerebellar architecture not only requires proper development but also long-term integrity to ensure accurate functioning. Developmental defects such as impaired neuronal migration or neurodegeneration are thus detrimental to the cerebellum and can result in movement disorders including ataxias. In this study, we identify FBXO41 as a novel CNS-specific F-box protein that localizes to the centrosome and the cytoplasm of neurons and demonstrate that cytoplasmic FBXO41 promotes neuronal migration. Interestingly, deletion of the FBXO41 gene results in a severely ataxic gait in mice, which show delayed neuronal migration of granule neurons in the developing cerebellum in addition to deformities and degeneration of the mature cerebellum. We show that FBXO41 is a critical factor, not only for neuronal migration in the cerebellum, but also for its long-term integrity.
authors.affiliation: Cellular and Molecular Neurobiology and Center for Nanoscale Microscopy and Molecular Physiology of the Brain, 37075 Göttingen, Germany, and International Max Planck Research School of Neurosciences, 37075 Göttingen, Germany.
authors.forename: Chaitali
authors.identifier: http://orcid.org/0000-0001-7682-8654
authors.initials: C
authors.lastname: Mukherjee
authors.affiliation: Cellular and Molecular Neurobiology and Center for Nanoscale Microscopy and Molecular Physiology of the Brain, 37075 Göttingen, Germany, and.
authors.forename: Anna
authors.initials: A
authors.lastname: Holubowska
authors.affiliation: Cellular and Molecular Neurobiology and.
authors.forename: Nicola
authors.initials: N
authors.lastname: Schwedhelm-Domeyer
authors.affiliation: Light Microscopy Facility, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Miso
authors.initials: M
authors.lastname: Mitkovski
authors.affiliation: Cellular and Molecular Neurobiology and.
authors.forename: Shih-Ju
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Cellular and Molecular Neurobiology and.
authors.forename: Madhuvanthi
authors.initials: M
authors.lastname: Kannan
authors.affiliation: Cellular and Molecular Neurobiology and.
authors.forename: Annika
authors.initials: A
authors.lastname: Matz
authors.affiliation: Cellular and Molecular Neurobiology and Center for Nanoscale Microscopy and Molecular Physiology of the Brain, 37075 Göttingen, Germany, and International Max Planck Research School of Neurosciences, 37075 Göttingen, Germany.
authors.forename: Mayur
authors.initials: M
authors.lastname: Vadhvani
authors.affiliation: Cellular and Molecular Neurobiology and Center for Nanoscale Microscopy and Molecular Physiology of the Brain, 37075 Göttingen, Germany, and stegmueller@em.mpg.de.
authors.forename: Judith
authors.initials: J
authors.lastname: Stegmüller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D044783:F-Box Proteins; C588009:FBXO41 protein, human; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins
keywords: F-box protein; ataxia; cerebellum; degeneration; neuronal migration