Increased dendritic complexity and axonal length in cultured mouse cortical neurons overexpressing methyl-CpG-binding protein MeCP2.
Rett syndrome is caused by loss-of-function mutations in the gene encoding the methyl DNA-binding factor MeCP2. As brain mass and neuronal complexity tend to be diminished in Rett patients, we tested whether MeCP2 directly influences the morphological complexity of developing neurons. Our results show that cultured mouse neurons overexpressing MeCP2beta (MECP2A) develop more complex morphologies, having longer axonal and dendritic processes, and an increased number of axonal and dendritic terminal endings. We then tested whether overexpressing a mutant form of MeCP2beta lacking its carboxyl terminus would elicit the same effects. Interestingly, while neurons overexpressing this mutant failed to enhance axonal and dendritic process elongation, the complexity of their axonal and dendritic processes remained significantly elevated. Taken together, these data support the hypothesis that MeCP2 directly regulates neuronal maturation and/or synaptogenesis, and provides evidence that MeCP2 may influence neuritic elongation and process branching through different mechanisms.
Jugloff
Denis G M
DG
Division of Cellular and Molecular Biology, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada, M5T 2S8.
Jung
Benjamin P
BP
Purushotham
Diana
D
Logan
Richard
R
Eubanks
James H
JH
D000818:Animals; D001369:Axons / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D048429:Cell Size; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D005260:Female; D051783:Methyl-CpG-Binding Protein 2; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011247:Pregnancy; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins