CDYL Deficiency Disrupts Neuronal Migration and Increases Susceptibility to Epilepsy

被引：40

作者：

Qin, Rui ^{[1
,2
]}

Cao, Shuai ^{[1
,2
]}

Lyu, Tianjie ^{[1
,2
]}

Qi, Cai ^{[1
,2
]}

Zhang, Weiguang ^{[3
]}

Wang, Yun ^{[1
,2
,4
]}

机构：

[1] Peking Univ, Minist Educ, Natl Hlth & Family Planning Commiss, Key Lab Neurosci,Sch Basic Med Sci,Neurosci Res I, Beijing 100191, Peoples R China

[2] Peking Univ, Minist Educ, Natl Hlth & Family Planning Commiss, Key Lab Neurosci,Sch Basic Med Sci,Dept Neurobiol, Beijing 100191, Peoples R China

[3] Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Anat Histol & Embryol, Beijing 100191, Peoples R China

[4] Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing 100871, Peoples R China

来源：

CELL REPORTS | 2017年 / 18卷 / 02期

基金：

中国国家自然科学基金;

关键词：

CEREBRAL-CORTEX; CELL-MIGRATION; REPRESSOR COMPLEX; RADIAL MIGRATION; CO-REPRESSOR; RHOA; MECHANISMS; INHIBITION; DISORDERS; BRAIN;

D O I：

10.1016/j.celrep.2016.12.043

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

During brain development, the correct migration of newborn neurons is one of the determinants of circuit formation, and neuronal migration defects may lead to neurological and psychiatric disorders. The molecular mechanisms underlying neuronal migration and related disorders are poorly understood. Here, we report that Chromodomain Y-like (CDYL) is critical for neuronal migration in mice. Knocking down CDYL caused neuronalmigration defects and disrupted both mobility and multipolar-to-bipolar transition of migrating neurons. We find that CDYL regulates neuronal migration by transcriptionally repressing RhoA. In addition, CDYL deficiency increased the excitability of cortical pyramidal neurons and the susceptibility of mice to convulsant-induced seizures. These results demonstrate that CDYL is a regulator of neuronal migration and shed light on the pathogenesis of seizure-related neurodevelopmental disorders.

引用

页码：380 / 390

页数：11

共 42 条

[1] Trekking across the brain: The journey of neuronal migration [J].

Ayala, Ramses ;

Shu, Tianzhi ;

Tsai, Li-Huei .

CELL, 2007, 128 (01) :29-43

[2] An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration [J].

Azzarelli, Roberta ;

Pacary, Emilie ;

Garg, Ritu ;

Garcez, Patricia ;

van den Berg, Debbie ;

Riou, Philippe ;

Ridley, Anne J. ;

Friedel, Roland H. ;

Parsons, Maddy ;

Guillemot, Francois .

NATURE COMMUNICATIONS, 2014, 5 :3405

[3] RNAi reveals doublecortin is required for radial migration in rat neocortex [J].

Bai, JL ;

Ramos, RL ;

Ackman, JB ;

Thomas, AM ;

Lee, RV ;

LoTurco, JJ .

NATURE NEUROSCIENCE, 2003, 6 (12) :1277-1283

[4] Wnt Signaling Regulates Multipolar-to-Bipolar Transition of Migrating Neurons in the Cerebral Cortex [J].

Boitard, Michael ;

Bocchi, Riccardo ;

Egervari, Kristof ;

Petrenko, Volodymyr ;

Viale, Beatrice ;

Gremaud, Stephane ;

Zgraggen, Eloisa ;

Salmon, Patrick ;

Kiss, Jozsef Z. .

CELL REPORTS, 2015, 10 (08) :1349-1361

[5] The GABAA Receptor as a Therapeutic Target for Neurodevelopmental Disorders [J].

Braat, Sien ;

Kooy, R. Frank .

NEURON, 2015, 86 (05) :1119-1130

[6] A Radial Glia-Specific Role of RhoA in Double Cortex Formation [J].

Cappello, Silvia ;

Boehringer, Christian R. J. ;

Bergami, Matteo ;

Conzelmann, Karl-Klaus ;

Ghanem, Alexander ;

Tomassy, Giulio Srubek ;

Arlotta, Paola ;

Mainardi, Marco ;

Allegra, Manuela ;

Caleo, Matteo ;

van Hengel, Jolanda ;

Brakebusch, Cord ;

Goetz, Magdalena .

NEURON, 2012, 73 (05) :911-924

[7] Cdyl: a new transcriptional co-repressor [J].

Caron, C ;

Pivot-Pajot, C ;

van Grunsven, LA ;

Col, E ;

Lestrat, C ;

Rousseaux, S ;

Khochbin, S .

EMBO REPORTS, 2003, 4 (09) :877-882

[8] Does subtle disturbance of neuronal migration contribute to schizophrenia and other neurodevelopmental disorders? Potential genetic mechanisms with possible treatment implications [J].

Deutsch, Stephen I. ;

Burket, Jessica A. ;

Katz, Elionora .

EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2010, 20 (05) :281-287

[9] Coupling of cell migration with neurogenesis by proneural bHLH factors [J].

Ge, WH ;

He, F ;

Kim, KJ ;

Blanchi, B ;

Coskun, V ;

Nguyen, L ;

Wu, XB ;

Zhao, J ;

Heng, JIT ;

Martinowich, K ;

Tao, JF ;

Wu, H ;

Castro, D ;

Sobeih, MM ;

Corfas, G ;

Gleeson, JG ;

Greenberg, ME ;

Guillemot, F ;

Sun, YE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (05) :1319-1324

[10] Neuronal migration disorders: from genetic diseases to developmental mechanisms [J].

Gleeson, JG ;

Walsh, CA .

TRENDS IN NEUROSCIENCES, 2000, 23 (08) :352-359

← 1 2 3 4 5 →