Australian Regenerative Medicine Institute, Monash University Clayton Campus, Clayton, Victoria, 3800, Australia.
Department of Human Anatomy and Cell Science, College of Medicine, University of Manitoba, Winnipeg, R3E 3P5, Canada.
Sci Rep. 2019 Mar 14;9(1):4420. doi: 10.1038/s41598-019-40734-z.
How diverse adult stem and progenitor populations regenerate tissue following damage to the brain is poorly understood. In highly regenerative vertebrates, such as zebrafish, radial-glia (RG) and neuro-epithelial-like (NE) stem/progenitor cells contribute to neuronal repair after injury. However, not all RG act as neural stem/progenitor cells during homeostasis in the zebrafish brain, questioning the role of quiescent RG (qRG) post-injury. To understand the function of qRG during regeneration, we performed a stab lesion in the adult midbrain tectum to target a population of homeostatic qRG, and investigated their proliferative behaviour, differentiation potential, and Wnt/β-catenin signalling. EdU-labelling showed a small number of proliferating qRG after injury (pRG) but that progeny are restricted to RG. However, injury promoted proliferation of NE progenitors in the internal tectal marginal zone (TMZi) resulting in amplified regenerative neurogenesis. Increased Wnt/β-catenin signalling was detected in TMZi after injury whereas homeostatic levels of Wnt/β-catenin signalling persisted in qRG/pRG. Attenuation of Wnt signalling suggested that the proliferative response post-injury was Wnt/β-catenin-independent. Our results demonstrate that qRG in the tectum have restricted capability in neuronal repair, highlighting that RG have diverse functions in the zebrafish brain. Furthermore, these findings suggest that endogenous stem cell compartments compensate lost tissue by amplifying homeostatic growth.
成人干细胞和祖细胞群体在大脑受损后如何再生组织尚不清楚。在高度再生的脊椎动物中，如斑马鱼，放射状胶质（RG）和神经上皮样（NE）干细胞/祖细胞有助于损伤后的神经元修复。然而，并非所有 RG 在斑马鱼大脑的体内平衡中都充当神经干细胞/祖细胞，这质疑了静息 RG（qRG）在损伤后的作用。为了了解 qRG 在再生过程中的功能，我们在成年中脑顶盖进行了刺伤损伤，以靶向一群体内平衡的 qRG，并研究了它们的增殖行为、分化潜力和 Wnt/β-连环蛋白信号传导。EdU 标记显示损伤后只有少量增殖的 qRG（pRG），但祖细胞仅限于 RG。然而，损伤促进了内部顶盖边缘区（TMZi）中的 NE 祖细胞的增殖，导致再生神经发生增加。损伤后在 TMZi 中检测到 Wnt/β-连环蛋白信号增加，而 qRG/pRG 中保持了体内平衡水平的 Wnt/β-连环蛋白信号。Wnt 信号的衰减表明损伤后的增殖反应是 Wnt/β-连环蛋白非依赖性的。我们的结果表明，顶盖中的 qRG 在神经元修复方面的能力有限，这强调了 RG 在斑马鱼大脑中具有多种功能。此外，这些发现表明内源性干细胞区室通过放大体内平衡生长来补偿丢失的组织。
