Institut Pasteur, Université Paris Cité, CNRS UMR3738, Zebrafish Neurogenetics Unit, Team supported by the Ligue Nationale Contre le Cancer, Paris 75015, France.
Sorbonne Université, Collège Doctoral, Paris F-75005, France.
Sci Adv. 2023 Sep;9(35):eadg7519. doi: 10.1126/sciadv.adg7519. Epub 2023 Sep 1.
The maintenance of neural stem cells (NSCs) in the adult brain depends on their activation frequency and division mode. Using long-term intravital imaging of NSCs in the zebrafish adult telencephalon, we reveal that apical surface area and expression of the Notch ligand DeltaA predict these NSC decisions. -negative NSCs constitute a bona fide self-renewing NSC pool and systematically engage in asymmetric divisions generating a self-renewing daughter, which regains the size and behavior of its mother, and a neurogenic daughter, eventually engaged in neuronal production following further quiescence-division phases. Pharmacological and genetic manipulations of Notch, DeltaA, and apical size further show that the prediction of activation frequency by apical size and the asymmetric divisions of NSCs are functionally independent of Notch. These results provide dynamic qualitative and quantitative readouts of NSC lineage progression in vivo and support a hierarchical organization of NSCs in differently fated subpopulations.
成年大脑中神经干细胞（NSCs）的维持依赖于它们的激活频率和分裂模式。通过对斑马鱼成年端脑 NSCs 的长期活体成像，我们揭示了顶表面积和 Notch 配体 DeltaA 的表达可以预测这些 NSC 决策。-阴性 NSCs 构成了一个真正的自我更新 NSC 池，并系统地进行不对称分裂，产生一个自我更新的子细胞，它恢复了其母细胞的大小和行为，以及一个神经发生的子细胞，最终在进一步的静止-分裂阶段后参与神经元产生。Notch、DeltaA 和顶表面积的药理学和遗传学操作进一步表明，顶表面积对激活频率的预测以及 NSCs 的不对称分裂在功能上与 Notch 无关。这些结果提供了体内 NSC 谱系进展的动态定性和定量读数，并支持 NSCs 在不同命运亚群中的分层组织。
