Genetic link between Cabeza, a Drosophila homologue of Fused in Sarcoma (FUS), and the EGFR signaling pathway
Genetic link between Cabeza, a Drosophila homologue of Fused in Sarcoma (FUS), and the EGFR signaling pathway
复制标题
Cabeza（肉瘤融合蛋白 (FUS) 的果蝇同源物）与 EGFR 信号通路之间的遗传联系
DOI：
10.1016/j.yexcr.2014.06.004
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yamaguchi M et al.
中科院分区：
文献类型：
--
作者：
Shimamura M;Nakagawa M;Yamaguchi M et al.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，导致进行性肌肉无力。已在家族性ALS中鉴定的融合肉瘤（FUS）是通常位于细胞核中的RNA结合蛋白。果蝇Cabeza（Caz）是一种aFU同源物，利用aGMR-GAL 4driver在果蝇成虫的眼盘和蛹视网膜中特异性敲除Caz，可以诱导果蝇复眼的异常形态，即粗糙眼表型。凋亡抑制因子P35的表达部分抑制了这一过程。敲除Caz对感光细胞的分化无明显影响。然而，免疫组化染色与抗体切割，标志着锥细胞显示这些和小眼的蛹视网膜融合。这些结果表明，Caz敲低诱导细胞凋亡，也抑制视锥细胞的分化，导致成人异常的眼睛形态。EGFR通路相关基因如rhomboid-1、rhomboid-3和mirror的突变抑制了Caz敲低诱导的粗糙眼表型。此外，therhomoboid-1突变挽救了在Caz敲除果蝇中观察到的视锥细胞和小眼的融合。结果表明，Caz负调控决定果蝇视锥细胞命运所需的EGFR信号通路。
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive muscular weakness. Fused in Sarcoma (FUS) that has been identified in familial ALS is an RNA binding protein that is normally localized in the nucleus. However, its function in vivo is not fully understood.Drosophilahas Cabeza (Caz) as aFUShomologue and specific knockdown of Caz in the eye imaginal disc and pupal retina using aGMR-GAL4driver was here found to induce an abnormal morphology of the adult compound eyes, a rough eye phenotype. This was partially suppressed by expression of the apoptosis inhibitor P35. Knockdown of Caz exerted no apparent effect on differentiation of photoreceptor cells. However, immunostaining with an antibody to Cut that marks cone cells revealed fusion of these and ommatidia of pupal retinae. These results indicate that Caz knockdown induces apoptosis and also inhibits differentiation of cone cells, resulting in abnormal eye morphology in adults. Mutation in EGFR pathway-related genes, such asrhomboid-1,rhomboid-3and mirror suppressed the rough eye phenotype induced by Caz knockdown. Moreover, therhomboid-1mutation rescued the fusion of cone cells and ommatidia observed in Caz knockdown flies. The results suggest that Caz negatively regulates the EGFR signaling pathway required for determination of cone cell fate inDrosophila.