Institute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao, China.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
EMBO Rep. 2023 Jan 9;24(1):e54984. doi: 10.15252/embr.202254984. Epub 2022 Nov 21.
Spinal cord injury (SCI) can cause long-lasting disability in mammals due to the lack of axonal regrowth together with the inability to reinitiate spinal neurogenesis at the injury site. Deciphering the mechanisms that regulate the proliferation and differentiation of neural progenitor cells is critical for understanding spinal neurogenesis after injury. Compared with mammals, zebrafish show a remarkable capability of spinal cord regeneration. Here, we show that Rassf7a, a member of the Ras-association domain family, promotes spinal cord regeneration after injury. Zebrafish larvae harboring a rassf7a mutation show spinal cord regeneration and spinal neurogenesis defects. Live imaging shows abnormal asymmetric neurogenic divisions and spindle orientation defects in mutant neural progenitor cells. In line with this, the expression of rassf7a is enriched in neural progenitor cells. Subcellular analysis shows that Rassf7a localizes to the centrosome and is essential for cell cycle progression. Our data indicate a role for Rassf7a in modulating spindle orientation and the proliferation of neural progenitor cells after spinal cord injury.
脊髓损伤 (SCI) 可导致哺乳动物出现持久残疾,这是因为轴突再生缺失,并且损伤部位无法重新启动脊髓神经发生。解析调控神经祖细胞增殖和分化的机制对于理解损伤后脊髓神经发生至关重要。与哺乳动物相比,斑马鱼表现出显著的脊髓再生能力。在这里,我们发现 Ras 相关结构域家族的成员 Rassf7a 可促进损伤后的脊髓再生。携带 rassf7a 突变的斑马鱼幼虫表现出脊髓再生和脊髓神经发生缺陷。活体成像显示突变神经祖细胞中存在异常的不对称神经发生分裂和纺锤体取向缺陷。与此一致的是,rassf7a 的表达富集在神经祖细胞中。亚细胞分析表明 Rassf7a 定位于中心体,对于细胞周期进程是必需的。我们的数据表明 Rassf7a 在调节脊髓损伤后纺锤体取向和神经祖细胞增殖方面发挥作用。