title: Altered microtubule dynamics in Mecp2-deficient astrocytes.
abstract: Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in the gene MECP2 encoding the methyl-CpG binding protein 2. This genetic disease affects predominantly girls and is characterized by a period of normal development that lasts for 8-18 months, followed by neurologic regression affecting both motor and mental abilities. Previous studies performed on brains from RTT subjects and Mecp2-deficient mice showed striking changes in neuronal maturation and dendritic arborization. Recently, we showed that expression of stathmin-like 2 (STMN2) was significantly reduced in fibroblasts from RTT patients, and similar results were obtained in the cerebellum of Mecp2-deficient mice. Because assembly and dynamics of microtubules are known to be modulated by STMN2, we studied microtubule dynamics in brain cells from Mecp2-deficient mice. We observed that Mecp2 deficiency affects microtubule dynamics in astrocytes from Mecp2-deficient mice. Our data reinforce the fact that the loss of Mecp2 in astrocytes may influence the onset and progression of RTT. These results imply that Mecp2 has a stabilizing role in microtubule dynamics and that Mecp2 deficiency, which is associated with STMN2 down-regulation, could lead to impaired microtubule stability, hence explaining the dendritic abnormalities observed in RTT brains.
authors.affiliation: Université Paris Descartes, CNRS UMR 8104, Institut Cochin, Laboratoire de Génétique des Maladies Neurodéveloppementales, Paris, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Nectoux
authors.forename: Cedrick
authors.initials: C
authors.lastname: Florian
authors.forename: Chloe
authors.initials: C
authors.lastname: Delepine
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi-Buisson
authors.forename: Malik
authors.initials: M
authors.lastname: Khelfaoui
authors.forename: Sophie
authors.initials: S
authors.lastname: Reibel
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D002531:Cerebellum; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D017711:Nonlinear Dynamics; D050777:Stathmin; D014162:Transfection
chemical_list: D002135:Calcium-Binding Proteins; C522423:EB3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D008869:Microtubule-Associated Proteins; D050777:Stathmin; C512849:Stmn2 protein, mouse; D049452:Green Fluorescent Proteins