Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, United States.
Department of Neurological Surgery, University of Washington, Seattle, United States.
Elife. 2020 Apr 3;9:e53777. doi: 10.7554/eLife.53777.
The hippocampal dentate gyrus (DG) is a unique brain region maintaining neural stem cells (NCSs) and neurogenesis into adulthood. We used multiphoton imaging to visualize genetically defined progenitor subpopulations in live slices across key stages of mouse DG development, testing decades old static models of DG formation with molecular identification, genetic-lineage tracing, and mutant analyses. We found novel progenitor migrations, timings, dynamic cell-cell interactions, signaling activities, and routes underlie mosaic DG formation. Intermediate progenitors (IPs, Tbr2+) pioneered migrations, supporting and guiding later emigrating NSCs (Sox9+) through multiple transient zones prior to converging at the nascent outer adult niche in a dynamic settling process, generating all prenatal and postnatal granule neurons in defined spatiotemporal order. IPs (Dll1+) extensively targeted contacts to mitotic NSCs (Notch active), revealing a substrate for cell-cell contact support during migrations, a developmental feature maintained in adults. Mouse DG formation shares conserved features of human neocortical expansion.
海马齿状回（DG）是一个独特的脑区，在成年期维持神经干细胞（NCSs）和神经发生。我们使用多光子成像在活切片中可视化遗传定义的祖细胞亚群，跨越小鼠 DG 发育的关键阶段，通过分子鉴定、遗传谱系追踪和突变体分析来测试几十年来 DG 形成的静态模型。我们发现了新的祖细胞迁移、时间、动态细胞-细胞相互作用、信号活动和途径，这些都是镶嵌性 DG 形成的基础。中间祖细胞（IPs，Tbr2+）率先迁移，通过多个短暂的过渡区支持和引导后来迁移的 NSCs（Sox9+），然后在一个动态的定居过程中汇聚到新形成的外成体龛，按照特定的时空顺序产生所有的产前和产后颗粒神经元。IPs（Dll1+）广泛靶向有丝分裂 NSCs（Notch 活性）的接触，揭示了迁移过程中细胞-细胞接触支持的基础，这是成年期维持的发育特征。小鼠 DG 的形成具有保守的人类新皮质扩张特征。
