Ewing sarcoma protein ewsr1 maintains mitotic integrity and proneural cell survival in the zebrafish embryo.
Ewing sarcoma protein ewsr1 maintains mitotic integrity and proneural cell survival in the zebrafish embryo.
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DOI：
10.1371/journal.pone.0000979
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发表时间：
2007-10-03
期刊：
影响因子：
3.7
通讯作者：
Hickstein DD
中科院分区：
文献类型：
--
作者：
Azuma M;Embree LJ;Sabaawy H;Hickstein DD
尤文肉瘤断点区1基因(EWSR1)，又称EWS，是不同肉瘤染色体易位的结果，与许多不同的配对基因融合。尽管EWSR1参与了这些不同的肉瘤，但野生型EWSR1的体内功能仍不清楚。我们鉴定了两个斑马鱼EWSR1同源基因ewsr1a和ewsr1b，并证明这两个基因在母体中表达，并在斑马鱼胚胎发育过程中普遍表达。Morpholino诱导两个基因的敲除导致斑马鱼EWSR1基因的有丝分裂缺陷，从蕾期(受精后10小时)开始出现多极或异常的有丝分裂纺锤体。随着有丝分裂纺锤体的异常，发育中的中枢神经系统(CNS)中P53介导的细胞凋亡导致受精后5天神经原细胞数量减少，神经元网络解体，胚胎死亡。EWSR1在Hela细胞中的siRNA沉默导致有丝分裂缺陷并伴有细胞死亡，表明EWSR1的作用在斑马鱼和人类之间是保守的。EWSR1在斑马鱼发育早期维持有丝分裂的完整性和原神经细胞的存活。
The Ewing sarcoma breakpoint region 1 gene (EWSR1), also known as EWS, is fused to a number of different partner genes as a result of chromosomal translocation in diverse sarcomas. Despite the involvement of EWSR1 in these diverse sarcomas, the in vivo function of wild type EWSR1 remains unclear. We identified two zebrafish EWSR1 orthologues, ewsr1a and ewsr1b, and demonstrate that both genes are expressed maternally, and are expressed ubiquitously throughout zebrafish embryonic development. Morpholino induced knockdown of both zebrafish ewsr1 genes led to mitotic defects with multipolar or otherwise abnormal mitotic spindles starting from the bud stage (10 hour post-fertilization (hpf)). The abnormalities in mitotic spindles were followed by p53-mediated apoptosis in the developing central nervous system (CNS) leading to a reduction in the number of proneural cells, disorganization of neuronal networks, and embryonic lethality by 5 days post-fertilization. siRNA silencing of EWSR1 in Hela cells resulted in mitotic defects accompanied by apoptotic cell death, indicating that the role of EWSR1 is conserved between zebrafish and human. Ewsr1 maintains mitotic integrity and proneural cell survival in early zebrafish development.
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