Azuma Mizuki, Embree Lisa J, Sabaawy Hatem, Hickstein Dennis D
Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS One. 2007 Oct 3;2(10):e979. doi: 10.1371/journal.pone.0000979.
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.
尤因肉瘤断点区域1基因（EWSR1），也称为EWS，在多种肉瘤中由于染色体易位而与许多不同的伙伴基因融合。尽管EWSR1参与了这些不同的肉瘤，但野生型EWSR1在体内的功能仍不清楚。
我们鉴定出两个斑马鱼EWSR1直系同源基因，ewsr1a和ewsr1b，并证明这两个基因在母体内表达，且在斑马鱼胚胎发育过程中普遍表达。吗啉代诱导的斑马鱼ewsr1基因敲低导致有丝分裂缺陷，从芽期（受精后10小时（hpf））开始出现多极或其他异常有丝分裂纺锤体。有丝分裂纺锤体的异常随后导致发育中的中枢神经系统（CNS）中p53介导的细胞凋亡，导致神经前体细胞数量减少、神经网络紊乱，并在受精后5天导致胚胎死亡。在Hela细胞中用小干扰RNA（siRNA）沉默EWSR1导致有丝分裂缺陷并伴有凋亡细胞死亡，表明EWSR1在斑马鱼和人类之间的作用是保守的。
Ewsr1在斑马鱼早期发育中维持有丝分裂完整性和神经前体细胞存活。
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