title: Vav3-deficient mice exhibit a transient delay in cerebellar development.
abstract: Vav3 is a guanosine diphosphate/guanosine triphosphate exchange factor for Rho/Rac GTPases that has been involved in functions related to the hematopoietic system, bone formation, cardiovascular regulation, angiogenesis, and axon guidance. We report here that Vav3 is expressed at high levels in Purkinje and granule cells, suggesting additional roles for this protein in the cerebellum. Consistent with this hypothesis, we demonstrate using Vav3-deficient mice that this protein contributes to Purkinje cell dendritogenesis, the survival of granule cells of the internal granular layer, the timely migration of granule cells of the external granular layer, and to the formation of the cerebellar intercrural fissure. With the exception of the latter defect, the dysfunctions found in Vav3(-/-) mice only occur at well-defined postnatal developmental stages and disappear, or become ameliorated, in older animals. Vav2-deficient mice do not show any of those defects. Using primary neuronal cultures, we show that Vav3 is important for dendrite branching, but not for primary dendritogenesis, in Purkinje and granule cells. Vav3 function in the cerebellum is functionally relevant, because Vav3(-/-) mice show marked motor coordination and gaiting deficiencies in the postnatal period. These results indicate that Vav3 function contributes to the timely developmental progression of the cerebellum.
authors.affiliation: Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas, University of Salamanca, Campus Unamuno, E-37007 Salamanca, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Quevedo
authors.forename: Vincent
authors.initials: V
authors.lastname: Sauzeau
authors.forename: Mauricio
authors.initials: M
authors.lastname: Menacho-Márquez
authors.forename: Antonio
authors.initials: A
authors.lastname: Castro-Castro
authors.forename: Xosé R
authors.initials: XR
authors.lastname: Bustelo
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism*; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology
chemical_list: D051567:Proto-Oncogene Proteins c-vav; C490565:Vav2 protein, mouse; C496622:Vav3 protein, mouse