Impaired cerebellar development and deficits in motor coordination in mice lacking the neuronal protein BM88/Cend1.
During nervous system development, neural progenitors arise in proliferative zones, then exit the cell cycle and differentiate as they migrate away from these zones. The neuronal protein BM88/Cend1 has been implicated in coordination of cell cycle exit and differentiation of neuronal precursors. To further elucidate its function we generated Cend1 knock-out mice and analyzed their phenotype during postnatal cerebellar development. Cend1(-/-) mice showed no overt abnormalities in the gross anatomy of the cerebellum or other brain regions. However, detailed analysis revealed alterations in cerebellar layering arising from increased proliferation of granule cell precursors, delayed radial granule cell migration and impaired Purkinje cell differentiation. Accordingly, expression of Patched1, cyclin D1, reelin and brain-derived neurotrophic factor, which correlate with morphological development of the cerebellum, was altered in Cend1(-/-) mice. The observed anatomical and molecular alterations were accompanied by deficits in motor behaviour. Our results suggest that Cend1 is required for normal cerebellar development.
Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, 11521 Athens, Greece.
Maria Christina
MC
Sergaki
Francois
F
Guillemot
Rebecca
R
Matsas
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D048430:Cell Shape / Q000235:genetics; D002478:Cells, Cultured; D002531:Cerebellum / Q000002:abnormalities* / Q000378:metabolism* / Q000473:pathology; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D019044:Image Cytometry; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009069:Movement Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D055495:Neurogenesis / Q000235:genetics; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D000091042:Reelin Protein; D016622:Silver Staining
D015415:Biomarkers; C496858:Cend1 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse