The N-Myc-DLL3 Cascade Is Suppressed by the Ubiquitin Ligase Huwe1 to Inhibit Proliferation and Promote Neurogenesis in the Developing Brain

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	The N-Myc-DLL3 Cascade Is Suppressed by the Ubiquitin Ligase Huwe1 to Inhibit Proliferation and Promote Neurogenesis in the Developing Brain
	Zhao XD 1; D'Arca D 1; Lim WK 2,3; Brahmachary M 3; Carro MS 1; Ludwig T 1,4; Cardo CC 4; Guillemot F 5; Aldape K 6; Califano A 2,3; Iavarone A1,4,8; Anna Lasorella A1,4,9; ai2102@columbia.edu ; al2179@columbia.edu
	2009
发表期刊	DEVELOPMENTAL CELL
卷号	17 期号:2 页码:210-221
摘要	Self-renewal and proliferation of neural stem cells and the decision to initiate neurogenesis are crucial events directing brain development. Here we show that the ubiquitin ligase Huwe1 operates upstream of the N-Myc-DLL3-Notch pathway to control neural stem cell activity and promote neurogenesis. Conditional inactivation of the Huwe1 gene in the mouse brain caused neonatal lethality associated with disorganization of the laminar patterning of the cortex. These defects stemmed from severe impairment of neurogenesis associated with uncontrolled expansion of the neural stem cell compartment. Loss- and gain-of-function experiments in the mouse cortex demonstrated that Huwe1 restrains proliferation and enables neuronal differentiation by suppressing the N-Myc-DLL3 cascade. Notably, human high-grade gliomas carry focal hemizygous deletions of the X-linked Huwe1 gene in association with amplification of the N-myc locus. Our results indicate that Huwe1 balances proliferation and neurogenesis in the developing brain and that this pathway is subverted in malignant brain tumors.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/7947
专题	科研共享资源
通讯作者	ai2102@columbia.edu; al2179@columbia.edu
作者单位	1.Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032 2.Department of Biomedical Informatics, Columbia University Medical Center, New York, New York 10032 3.Center for Computational Biology and Bioinformatics, Columbia University Medical Center, New York, New York 10032 4.Department of Pathology, Columbia University Medical Center, New York, New York 10032 5.Division of Molecular Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom 6.Department of Pathology, M.D. Anderson Cancer Center, Houston, Texas 77030 7.** 8.Department of Neurology, Columbia University Medical Center, New York, New York 10032 9.Department of Pediatrics, Columbia University Medical Center, New York, New York 10032
推荐引用方式 GB/T 7714	Zhao XD,D'Arca D,Lim WK,et al. The N-Myc-DLL3 Cascade Is Suppressed by the Ubiquitin Ligase Huwe1 to Inhibit Proliferation and Promote Neurogenesis in the Developing Brain[J]. DEVELOPMENTAL CELL,2009,17(2):210-221.
APA	Zhao XD.,D'Arca D.,Lim WK.,Brahmachary M.,Carro MS.,...&al2179@columbia.edu.(2009).The N-Myc-DLL3 Cascade Is Suppressed by the Ubiquitin Ligase Huwe1 to Inhibit Proliferation and Promote Neurogenesis in the Developing Brain.DEVELOPMENTAL CELL,17(2),210-221.
MLA	Zhao XD,et al."The N-Myc-DLL3 Cascade Is Suppressed by the Ubiquitin Ligase Huwe1 to Inhibit Proliferation and Promote Neurogenesis in the Developing Brain".DEVELOPMENTAL CELL 17.2(2009):210-221.

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2014070710.pdf（2219KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文