title: Developmental and maintenance defects in Rett syndrome neurons identified by a new mouse staging system in vitro.
abstract: Rett Syndrome (RTT) is a neurodevelopmental disorder associated with intellectual disability, mainly caused by loss-of-function mutations in the MECP2 gene. RTT brains display decreased neuronal size and dendritic arborization possibly caused by either a developmental failure or a deficit in the maintenance of dendritic arbor structure. To distinguish between these two hypotheses, the development of Mecp2-knockout mouse hippocampal neurons was analyzed in vitro. Since a staging system for the in vitro development of mouse neurons was lacking, mouse and rat hippocampal neurons development was compared between 1-15 days in vitro (DIV) leading to a 6-stage model for both species. Mecp2-knockout hippocampal neurons displayed reduced growth of dendritic branches from stage 4 (DIV4) onwards. At stages 5-6 (DIV9-15), synapse number was lowered in Mecp2-knockout neurons, suggesting increased synapse elimination. These results point to both a developmental and a maintenance setback affecting the final shape and function of neurons in RTT.
authors.affiliation: Department of Life Sciences, BRAIN Center for Neuroscience, University of Trieste Trieste, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Baj
authors.affiliation: Department of Life Sciences, BRAIN Center for Neuroscience, University of Trieste Trieste, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Patrizio
authors.affiliation: Department of Life Sciences, BRAIN Center for Neuroscience, University of Trieste Trieste, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Montalbano
authors.affiliation: Department of Life Sciences, BRAIN Center for Neuroscience, University of Trieste Trieste, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Sciancalepore
authors.affiliation: Department of Life Sciences, BRAIN Center for Neuroscience, University of Trieste Trieste, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Tongiorgi
keywords: Dendrites; Dendritic Spines; Neuronal morphology; Rett Syndrome; hippocampal neurons; neurodevelopment; staging system