Deficiency of smarcal1 causes cell cycle arrest and developmental abnormalities in zebrafish

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	Deficiency of smarcal1 causes cell cycle arrest and developmental abnormalities in zebrafish
	Du, Jiulin
刊名	DEVELOPMENTAL BIOLOGY
	2010
卷号	339 期号:1 页码:89-100
关键词	Cell cycle Chromatin remodeling Development Schimke Immuno-Osseous Dysplasia smarcal1 Apoptosis IMMUNO-OSSEOUS DYSPLASIA HUMAN-DISEASE EMBRYONIC HEMATOPOIESIS TRANSCRIPTION FACTORS E2F FAMILY T-CELL EXPRESSION MODEL GENES DIFFERENTIATION
ISSN号	0012-1606
通讯作者	Huang, C (reprint author), Shanghai Univ Tradit Chinese Med, Sch Pharm, 1200 Cailun Rd, Shanghai 201203, Peoples R China,chuang@sibs.ac.cn ; forestdu@ion.ac.cn
英文摘要	Mutations in SMARCAL1 cause Schimke Immuno-Osseous Dysplasia (SIOD), an autosomal recessive multisystem developmental disease characterized by growth retardation, T-cell deficiency, bone marrow failure, anemia and renal failure. SMARCAL1 encodes an ATP-driven annealing helicase. However, the biological function of SMARCAL1 and the molecular basis of SIOD remain largely unclear. In this work, we cloned the zebrafish homologue of the human SMARCAL1 gene and found that smarcal1 regulated cell cycle progression. Morpholino knockdown of smarcal1 in zebrafish recapitulated developmental abnormalities in SIOD patients, including growth retardation, craniofacial abnormality, and haematopoietic and vascular defects. Lack of smarcal1 caused G0/G1 cell cycle arrest and induced cell apoptosis. Furthermore, using Electrophoretic Mobility Shift Assay and reporter assay, we found that SMARCAL1 was transcriptionally inhibited by E2F6, an important cell cycle regulator. Over-expression of E2F6 in zebrafish embryos reduced the expression of smarcal1 mRNA and induced developmental defects similar to those in smarcal1 morphants. These results suggest that SIOD may be caused by defects in cell cycle regulation. Our study provides a model of SIOD and reveals its cellular and molecular bases. (C) 2009 Elsevier Inc. All rights reserved.
学科主题	Developmental Biology
收录类别	SCI
资助信息	National Key Basic Research[2007CB947100, 2006CB806605, 2006CB943802]; Shanghai government[06dj14010, 07pj14107]
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1602]
专题	上海神经科学研究所_神经所(总) 上海神经科学研究所_感觉整合与行为研究组
推荐引用方式 GB/T 7714	Du, Jiulin. Deficiency of smarcal1 causes cell cycle arrest and developmental abnormalities in zebrafish[J]. DEVELOPMENTAL BIOLOGY,2010,339(1):89-100.
APA	Du, Jiulin.(2010).Deficiency of smarcal1 causes cell cycle arrest and developmental abnormalities in zebrafish.DEVELOPMENTAL BIOLOGY,339(1),89-100.
MLA	Du, Jiulin."Deficiency of smarcal1 causes cell cycle arrest and developmental abnormalities in zebrafish".DEVELOPMENTAL BIOLOGY 339.1(2010):89-100.