Tcf4 Controls Neuronal Migration of the Cerebral Cortex through Regulation of Bmp7

被引：25

作者：

Chen, Tianda ^{[1
,2
,3
]}

Wu, Qinwei ^{[1
,4
,5
]}

Zhang, Yang ^{[1
,2
,3
]}

Lu, Tianlan ^{[1
,2
,3
]}

Yue, Weihua ^{[1
,2
,3
]}

Zhang, Dai ^{[1
,2
,3
,5
,6
]}

机构：

[1] Peking Univ, Hosp 6, Inst Mental Hlth, Beijing, Peoples R China

[2] Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing, Peoples R China

[3] Peking Univ, Natl Clin Res Ctr Mental Disorders, Beijing, Peoples R China

[4] Peking Univ, Acad Adv Interdisciplinary Studies, Beijing, Peoples R China

[5] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China

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

来源：

FRONTIERS IN MOLECULAR NEUROSCIENCE | 2016年 / 9卷

基金：

中国国家自然科学基金; 北京市自然科学基金;

关键词：

schizophrenia; brain development; neuronal migration; TCF4; Bmp7; PITT-HOPKINS-SYNDROME; TRANSCRIPTION FACTOR; DIFFERENTIATION; SCHIZOPHRENIA; PROGENITORS; PROTEINS; GENES; CELLS; E2-2;

D O I：

10.3389/fnmol.2016.00094

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: Transcription factor 4 (TCF4) is found to be associated with schizophrenia. TCF4 mutations also cause Pitt-Hopkins Syndrome, a neurodevelopmental disorder associated with severe mental retardation. However, the function of TCF4 during brain development remains unclear. Results: Here, we report that Tcf4 is expressed in the developing cerebral cortex. In utero suppression of Tcf4 arrested neuronal migration, leading to accumulation of ectopic neurons in the intermediate zone. Knockdown of Tcf4 impaired leading process formation. Furthermore, Bone Morphogenetic Protein 7 (Bmp7) is upregulated in Tcf4-deficient neurons. In vivo gain of function and rescue experiments demonstrated that Bmp7 is the major downstream effector of Tcf4 required for neuronal migration. Conclusion: Thus, we have uncovered a new Tcf4/Bmp7-dependent mechanism underlying neuronal migration, and provide insights into the pathogenesis of neurodevelopmental disorders.

引用

页数：9

共 27 条

[1] A Comprehensive Family-Based Replication Study of Schizophrenia Genes [J].

Aberg, Karolina A. ;

Liu, Youfang ;

Bukszar, Jozsef ;

McClay, Joseph L. ;

Khachane, Amit N. ;

Andreassen, Ole A. ;

Blackwood, Douglas ;

Corvin, Aiden ;

Djurovic, Srdjan ;

Gurling, Hugh ;

Ophoff, Roel ;

Pato, Carlos N. ;

Pato, Michele T. ;

Riley, Brien ;

Webb, Todd ;

Kendler, Kenneth ;

O'Donovan, Mick ;

Craddock, Nick ;

Kirov, George ;

Owen, Mike ;

Rujescu, Dan ;

St Clair, David ;

Werge, Thomas ;

Hultman, Christina M. ;

Delisi, Lynn E. ;

Sullivan, Patrick ;

van den Oord, Edwin J. .

JAMA PSYCHIATRY, 2013, 70 (06) :573-581

[2] BDNF/MAPK/ERK-Induced BMP7 Expression in the Developing Cerebral Cortex Induces Premature Radial Glia Differentiation and Impairs Neuronal Migration [J].

Alberto Ortega, Juan ;

Alcantara, Soledad .

CEREBRAL CORTEX, 2010, 20 (09) :2132-2144

[3] Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction [J].

Amiel, Jeanne ;

Rio, Marlene ;

de Pontual, Loic ;

Redon, Richard ;

Malan, Valerie ;

Boddaert, Nathalie ;

Plouin, Perrine ;

Carter, Nigel P. ;

Lyonnet, Stanislas ;

Munnich, Arnold ;

Colleaux, Laurence .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (05) :988-993

[4] TCF4, Schizophrenia, and Pitt-Hopkins Syndrome [J].

Blake, Derek J. ;

Forrest, Marc ;

Chapman, Ria M. ;

Tinsley, Caroline L. ;

O'Donovan, Michael C. ;

Owen, Michael J. .

SCHIZOPHRENIA BULLETIN, 2010, 36 (03) :443-447

[5] Severe mental retardation with breathing abnormalities (Pitt-Hopkins syndrome) is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4 [J].

Brockschmidt, Antje ;

Todt, Unda ;

Ryu, Soojin ;

Hoischen, Alexander ;

Landwehr, Christina ;

Birnbaum, Stefanie ;

Frenck, Wilhelm ;

Radlwimmer, Bernhard ;

Lichter, Peter ;

Engels, Hartmut ;

Driever, Wolfgang ;

Kubisch, Christian ;

Weber, Ruthild G. .

HUMAN MOLECULAR GENETICS, 2007, 16 (12) :1488-1494

[6] The Retinoblastoma Protein Selectively Represses E2F1 Targets via a TAAC DNA Element during Cellular Senescence [J].

Chen, Tianda ;

Xue, Lixiang ;

Niu, Jing ;

Ma, Liwei ;

Li, Na ;

Cao, Xiaoxiao ;

Li, Qian ;

Wang, Meng ;

Zhao, Wenting ;

Li, Guodong ;

Wang, Jiamu ;

Tong, Tanjun .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (44) :37540-37551

[7] Neurog1 and Neurog2 Control Two Waves of Neuronal Differentiation in the Piriform Cortex [J].

Dixit, Rajiv ;

Wilkinson, Grey ;

Cancino, Gonzalo I. ;

Shaker, Tarek ;

Adnani, Lata ;

Li, Saiqun ;

Dennis, Daniel ;

Kurrasch, Deborah ;

Chan, Jennifer A. ;

Olson, Eric C. ;

Kaplan, David R. ;

Zimmer, Celine ;

Schuurmans, Carol .

JOURNAL OF NEUROSCIENCE, 2014, 34 (02) :539-553

[8]

EINARSON MB, 1995, MOL CELL BIOL, V15, P4175

[9] E-proteins orchestrate the progression of neural stem cell differentiation in the postnatal forebrain [J].

Fischer, Bruno ;

Azim, Kasum ;

Hurtado-Chong, Anahi ;

Ramelli, Sandra ;

Fernandez, Maria ;

Raineteau, Olivier .

NEURAL DEVELOPMENT, 2014, 9 :23

[10] The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors [J].

Flora, Adriano ;

Garcia, Jesus J. ;

Thaller, Christina ;

Zoghbi, Huda Y. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (39) :15382-15387

← 1 2 3 →