Department of Biology, University of Virginia, Charlottesville, United States.
Elife. 2024 Feb 23;12:RP88565. doi: 10.7554/eLife.88565.
Neuroblasts in divide asymmetrically, sequentially expressing a series of intrinsic factors to generate a diversity of neuron types. These intrinsic factors known as temporal factors dictate timing of neuroblast transitions in response to steroid hormone signaling and specify early versus late temporal fates in neuroblast neuron progeny. After completing their temporal programs, neuroblasts differentiate or die, finalizing both neuron number and type within each neuroblast lineage. From a screen aimed at identifying genes required to terminate neuroblast divisions, we identified Notch and Notch pathway components. When Notch is knocked down, neuroblasts maintain early temporal factor expression longer, delay late temporal factor expression, and continue dividing into adulthood. We find that Delta, expressed in cortex glia, neuroblasts, and after division, their GMC progeny, regulates neuroblast Notch activity. We also find that Delta in neuroblasts is expressed high early, low late, and is controlled by the intrinsic temporal program: early factor Imp promotes Delta, late factors Syp/E93 reduce Delta. Thus, in addition to systemic steroid hormone cues, forward lineage progression is controlled by local cell-cell signaling between neuroblasts and their cortex glia/GMC neighbors: Delta transactivates Notch in neuroblasts bringing the early temporal program and early temporal factor expression to a close.
神经母细胞以不对称的方式分裂,依次表达一系列内在因素,从而产生多种神经元类型。这些内在因素被称为时间因素,决定了神经母细胞在类固醇激素信号作用下的转换时间,并决定了神经母细胞神经元后代的早期和晚期时间命运。完成其时间程序后,神经母细胞会分化或死亡,从而确定每个神经母细胞谱系中的神经元数量和类型。我们从一个旨在鉴定终止神经母细胞分裂所需基因的筛选中发现了 Notch 和 Notch 通路成分。当 Notch 被敲低时,神经母细胞会更长时间地保持早期时间因子的表达,延迟晚期时间因子的表达,并持续分裂到成年期。我们发现,在皮质胶质细胞、神经母细胞中表达的 Delta,以及分裂后其 GMC 后代,调节神经母细胞 Notch 活性。我们还发现,神经母细胞中的 Delta 早期高表达,晚期低表达,并且受内在时间程序的控制:早期因子 Imp 促进 Delta 的表达,晚期因子 Syp/E93 降低 Delta 的表达。因此,除了系统的类固醇激素信号外,前体细胞的进展还受到神经母细胞与其皮质胶质细胞/GMC 邻居之间的局部细胞间信号的控制:Delta 在神经母细胞中转录激活 Notch,使早期时间程序和早期时间因子的表达接近尾声。