title: X-linked microtubule-associated protein, Mid1, regulates axon development.
abstract: Opitz syndrome (OS) is a genetic neurological disorder. The gene responsible for the X-linked form of OS, Midline-1 (MID1), encodes an E3 ubiquitin ligase that regulates the degradation of the catalytic subunit of protein phosphatase 2A (PP2Ac). However, how Mid1 functions during neural development is largely unknown. In this study, we provide data from in vitro and in vivo experiments suggesting that silencing Mid1 in developing neurons promotes axon growth and branch formation, resulting in a disruption of callosal axon projections in the contralateral cortex. In addition, a similar phenotype of axonal development was observed in the Mid1 knockout mouse. This defect was largely due to the accumulation of PP2Ac in Mid1-depleted cells as further down-regulation of PP2Ac rescued the axonal phenotype. Together, these data demonstrate that Mid1-dependent PP2Ac turnover is important for normal axonal development and that dysregulation of this process may contribute to the underlying cause of OS.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Tingjia
authors.initials: T
authors.lastname: Lu
authors.forename: Renchao
authors.initials: R
authors.lastname: Chen
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Cox
authors.forename: Randal X
authors.initials: RX
authors.lastname: Moldrich
authors.forename: Nyoman
authors.initials: N
authors.lastname: Kurniawan
authors.forename: Guohe
authors.initials: G
authors.lastname: Tan
authors.forename: Jo K
authors.initials: JK
authors.lastname: Perry
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.forename: Perry F
authors.initials: PF
authors.lastname: Bartlett
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Mingyue
authors.initials: M
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Xiong
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology* / Q000254:growth & development*; D002972:Cleft Palate / Q000503:physiopathology; D004947:Esophagus / Q000002:abnormalities / Q000503:physiopathology; D055785:Gene Knockdown Techniques; D040181:Genetic Diseases, X-Linked / Q000503:physiopathology; D020439:Growth Cones / Q000502:physiology*; D006972:Hypertelorism / Q000503:physiopathology; D007021:Hypospadias / Q000503:physiopathology; D015151:Immunoblotting; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D059008:Time-Lapse Imaging; D044767:Ubiquitin-Protein Ligases
chemical_list: D011506:Proteins; C109037:Mid1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D054648:Protein Phosphatase 2