斑马鱼脑部具有分布广泛的干细胞富集区和神经发生区，在经受严重的创伤性损伤后，胶质细胞前体细胞被刺激从而进行分裂和分化，弥补损失的神经元，实现自动修复。利用和人类基因组具有极高同源性的斑马鱼，研究斑马鱼脑损伤后，相同分子所产生的差异性功能对于探讨人类脑损伤后的修复治疗可能起到重要的参考作用。mcam，黑色素瘤细胞黏附分子，被临床应用作为肿瘤检验标记分子，介导细胞间的粘附作用。我们的前期结果发现斑马鱼端脑损伤后，mcam的表达明显上调，且高表达于神经发生区。那么mcam在斑马鱼脑损伤后的高表达是否与损伤修复过程中所发生的一系列再生性神经发生进程相关？本项目拟利用斑马鱼端脑损伤模型，辅以多种转基因斑马鱼来阐明mcam在分子水平、细胞水平、整体动物的发育状态和行为学水平上对于损伤后再生和修复的影响。该项目的完成对于进一步探究人类中枢神经系统的可再生性具有重要的科学价值和指导意义。

The adult neurogenic capacity of zebrafish is due to widespread stem cell niches and the neurogenic regions located in the brain. zebrafish brains can regenerate severe traumatic brain injuries, during which glial progenitors are stimulated to divide and replenish lost neurons. Using the character of zebrafish with high homology with human, we could make a matched research of the different functin of the same gene, which would play an important reference role in investigating the repairment process in human. mcam, melanoma cell adhesion molecule, which is involved in the adhesion between cells, is used as a tumor marker in clinic. Our preliminary results showed that mcam expression increased after telencephalon injury in zebrafish, which was enriched in neurogenesis zone. Then whether the high expression of mcam after TBI of zebrafish is correlated with the regenerative neurogenesis process happened in the period of repairment. Our research, combining with several transgenic zebrafish, is constructed based on telencephalon injury model to clarify the effect of mcam on regeneration and repair after injury at the molecular , cell level, development status of animals and behavior. The completion of this project would have important scientific value and guiding significance to further explore renewable of the human central nervous system.

创伤性脑损伤是导致死亡和残疾的最主要的原因。与哺乳动物不同，斑马鱼端脑背侧的神经前体细胞展现了放射状胶质细胞（RGC）的表型，损伤后可以诱导再生性神经发生过程。基于斑马鱼损伤前后基因芯片分析，我们发现一黑色素瘤细胞黏附分子，mcam，被临床应用作为肿瘤检验标记分子。在本基金的资助下，我们构建斑马鱼端脑损伤模型，探究mcam是否参与再生性神经发生过程及在损伤修复中起到的作用。在我们的研究中，发现斑马鱼端脑损伤后，mcam的表达明显上调，且高表达于神经发生区，mcam的表达与损伤后神经元的凋亡相关。此外在体外细胞系中，发现mcam可能通过调节atf3的表达变化来介导神经元的凋亡事件。这些研究都指示mcam可能在神经系统损伤修复中起到重要作用。在斑马鱼的胚胎发育过程中，干扰mcam功能表达后，斑马鱼胚胎发育畸形，表明mcam在斑马鱼胚胎发育过程中也发挥着至关重要的作用。对于斑马鱼和人类脑损伤后，相同分子所产生的差异性功能在再生能力的对比性研究至关重要。我们的这些研究为临床神经性疾病和神经系统损伤的检测和预后包括治疗提供了坚实的实验数据和理论基础。本项目共发表2篇SCI 论文，培养1名研究生。