Ankrd11 Is a Chromatin Regulator Involved in Autism that Is Essential for Neural Development

被引：125

作者：

Gallagher, Denis ^{[1
,3
]}

Voronova, Anastassia ^{[1
]}

Zander, Mark A. ^{[1
]}

Cancino, Gonzalo I. ^{[1
]}

Bramall, Alexa ^{[1
]}

Krause, Matthew P. ^{[1
]}

Abad, Clemer ^{[4
,5
]}

Tekin, Mustafa ^{[4
,5
]}

Neilsen, Paul M. ^{[6
]}

Callen, David F. ^{[7
]}

Scherer, Stephen W. ^{[2
,8
]}

Keller, Gordon M. ^{[3
,9
]}

Kaplan, David R. ^{[1
,8
]}

Walz, Katherina ^{[4
,5
]}

Miller, Freda D. ^{[1
,3
,8
,10
]}

机构：

[1] Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 1L7, Canada

[2] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1L7, Canada

[3] Univ Hlth Network, McEwen Ctr Regenerat Med, Toronto, ON M5G 1L7, Canada

[4] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn Dept Human Genet, Miami, FL 33136 USA

[5] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA

[6] Swinburne Univ Technol, Kuching 93350, Sarawak, Malaysia

[7] Univ Adelaide, Ctr Personalised Canc Med, Adelaide, SA 5000, Australia

[8] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X5, Canada

[9] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1X5, Canada

[10] Univ Toronto, Dept Physiol, Toronto, ON M5G 1X5, Canada

来源：

DEVELOPMENTAL CELL | 2015年 / 32卷 / 01期

关键词：

ANKYRIN REPEATS; INTELLECTUAL DISABILITY; HISTONE DEACETYLASES; SPECTRUM DISORDER; MEMORY FORMATION; KBG SYNDROME; MOUSE MODEL; MUTATIONS; IDENTIFICATION; DIFFERENTIATION;

D O I：

10.1016/j.devcel.2014.11.031

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin and colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knock-down-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial chromatin regulator that controls histone acetylation and gene expression during neural development, thereby providing a likely explanation for its association with cognitive dysfunction and ASD.

引用

页码：31 / 42

页数：12

共 38 条

[1] An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda [J].

Barbaric, Ivana ;

Perry, Mark J. ;

Dear, T. Neil ;

Da Costa, Alexandra Rodrigues ;

Salopek, Daniela ;

Marusic, Ana ;

Hough, Tertius ;

Wells, Sara ;

Hunter, A. Jackie ;

Cheeseman, Michael ;

Brown, Steve D. M. .

PHYSIOLOGICAL GENOMICS, 2008, 32 (03) :311-321

[2] Evidence that embryonic the onset of cortical neurons regulate gliogenesis via cardiotrophin-1 [J].

Barnabé-Heider, F ;

Wasylnka, JA ;

Fernandes, KJL ;

Porsche, C ;

Sendtner, M ;

Kaplan, DR ;

Miller, FD .

NEURON, 2005, 48 (02) :253-265

[3] Virtual Ligand Screening of the p300/CBP Histone Acetyltransferase: Identification of a Selective Small Molecule Inhibitor [J].

Bowers, Erin M. ;

Yan, Gai ;

Mukherjee, Chandrani ;

Orry, Andrew ;

Wang, Ling ;

Holbert, Marc A. ;

Crump, Nicholas T. ;

Hazzalin, Catherine A. ;

Liszczak, Glen ;

Yuan, Hua ;

Larocca, Cecilia ;

Saldanha, S. Adrian ;

Abagyan, Ruben ;

Sun, Yan ;

Meyers, David J. ;

Marmorstein, Ronen ;

Mahadevan, Louis C. ;

Alani, Rhoda M. ;

Cole, Philip A. .

CHEMISTRY & BIOLOGY, 2010, 17 (05) :471-482

[4] p63 Regulates Adult Neural Precursor and Newly Born Neuron Survival to Control Hippocampal-Dependent Behavior [J].

Cancino, Gonzalo I. ;

Yiu, Adelaide P. ;

Fatt, Michael P. ;

Dugani, Chandrasagar B. ;

Flores, Elsa R. ;

Frankland, Paul W. ;

Josselyn, Sheena A. ;

Miller, Freda D. ;

Kaplan, David R. .

JOURNAL OF NEUROSCIENCE, 2013, 33 (31) :12569-+

[5] Absence of Preference for Social Novelty and Increased Grooming in Integrin β3 Knockout Mice: Initial Studies and Future Directions [J].

Carter, Michelle D. ;

Shah, Charisma R. ;

Muller, Christopher L. ;

Crawley, Jacqueline N. ;

Carneiro, Ana M. D. ;

Veenstra-VanderWeele, Jeremy .

AUTISM RESEARCH, 2011, 4 (01) :57-67

[6] Neural Stem Cell Differentiation Is Dictated by Distinct Actions of Nuclear Receptor Corepressors and Histone Deacetylases [J].

Castelo-Branco, Goncalo G ;

Lilja, Tobias ;

Wallenborg, Karolina ;

Falcao, Ana M. ;

Marques, Sueli C. ;

Gracias, Aileen ;

Solum, Derek ;

Paap, Ricardo ;

Walfridsson, Julian ;

Teixeira, Ana I. ;

Rosenfeld, Michael G. ;

Jepsen, Kristen ;

Hermanson, Ola .

STEM CELL REPORTS, 2014, 3 (03) :502-515

[7] Don't Look: Growing Clonal Versus Nonclonal Neural Stem Cell Colonies [J].

Coles-Takabe, Brenda L. K. ;

Brain, Ian ;

Purpura, Kelly A. ;

Karpowicz, Phillip ;

Zandstra, Peter W. ;

Morshead, Cindi M. ;

Van der Kooy, Derek .

STEM CELLS, 2008, 26 (11) :2938-2944

[8] Social approach behaviors in oxytocin knockout mice: Comparison of two independent lines tested in different laboratory environments [J].

Crawley, Jacqueline N. ;

Chen, Thomas ;

Puri, Amit ;

Washburn, Richard ;

Sullivan, Timothy L. ;

Hill, Joanna M. ;

Young, Nancy B. ;

Nadler, Jessica J. ;

Moy, Sheryl S. ;

Young, Larry J. ;

Caldwell, Heather K. ;

Young, W. Scott .

NEUROPEPTIDES, 2007, 41 (03) :145-163

[9] Genetic architecture in autism spectrum disorder [J].

Devlin, Bernie ;

Scherer, Stephen W. .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2012, 22 (03) :229-237

[10] Transient Maternal IL-6 Mediates Long-Lasting Changes in Neural Stem Cell Pools by Deregulating an Endogenous Self-Renewal Pathway [J].

Gallagher, Denis ;

Norman, Andreea A. ;

Woodard, Cameron L. ;

Yang, Guang ;

Gauthier-Fisher, Andree ;

Fujitani, Masashi ;

Vessey, John P. ;

Cancino, Gonzalo I. ;

Sachewsky, Nadia ;

Woltjen, Knut ;

Fatt, Michael P. ;

Morshead, Cindi M. ;

Kaplan, David R. ;

Miller, Freda D. .

CELL STEM CELL, 2013, 13 (05) :564-576

← 1 2 3 4 →