Abstract：
Mfge8, a secreted glycoprotein, is a key molecule that mediates the phagocytosis of apoptotic cells. Previous research reported that Mfge8 is critical for the proliferation and differentiation of radial glial cells (RGCs) in the dentate gyrus of adult mice. The treatment of Mfge8 is also beneficial for the repair of central nervous system (CNS) injury after cerebral ischemia. This study aimed to investigate whether the expression of mfge8a in zebrafish embryos was associated with the development of CNS and larval behavior. We found that zebrafish mfge8a was initially expressed at 48 hpf, and its expression was gradually increased in the ventricular zone. Knocking down mfge8a with antisense morpholino oligonucleotides impaired both spontaneous and photoinduced swimming locomotion in the behavioral tests. The neurogenesis analysis in telencephalon showed that mfge8a morphants excessively promoted neural differentiation over self-renewal after RGCs division, and consequently depleted proliferative RGC population during early neurogenesis. Furthermore, downregulation of mfge8a was shown to alter the expression patterns of genes associated with Notch signaling pathway. Our results demonstrated that mfge8a is involved in the maintenance of the progenitor identity of RGCs in embryonic zebrafish brain through regulating Notch signaling pathway, thereby contributing to consistent neurogenesis and locomotor development.
摘要：
Mfge8，一种分泌的糖蛋白，是介导凋亡细胞吞噬的关键分子。先前的研究报道，Mfge8对成年小鼠齿状回中放射状神经胶质细胞（RGCs）的增殖和分化至关重要。Mfge8的医治还有益于脑缺血后中枢神经体系(CNS)毁伤的修复。本研究旨在探讨mfge8a在斑马鱼胚胎中的表达是否与中枢神经系统发育和幼虫行为有关。我们发现斑马鱼mfge8a最初在48hpf表达，其在心室区的表达逐渐增加。在行为测试中，用反义吗啉代寡核苷酸敲除mfge8a会损害自发和光诱导的游泳运动。端脑的神经发生分析表明，mfge8a形态在RGCs分裂后过度促进神经分化而不是自我更新，并因此在早期神经发生过程中减少了增殖性RGC群体。此外，mfge8a的下调被证明会改变与Notch信号通路相关的基因的表达模式。我们的结果表明，mfge8a通过调节Notch信号通路参与维持胚胎斑马鱼大脑中RGCs的祖细胞身份，从而有助于一致的神经发生和运动发育。
