Sood Chhavi, Nahid Md Ausrafuggaman, Branham Kendall R, Pahl Matthew C, Doyle Susan E, Siegrist Sarah E
bioRxiv. 2023 Sep 15:2023.03.28.534626. doi: 10.1101/2023.03.28.534626.
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.
神经母细胞不对称分裂,依次表达一系列内在因子以产生多种神经元类型。这些被称为时间因子的内在因子决定了神经母细胞响应类固醇激素信号转导而发生转变的时间,并确定神经母细胞神经元后代的早期与晚期时间命运。在完成其时间程序后,神经母细胞分化或死亡,从而确定每个神经母细胞谱系内的神经元数量和类型。通过旨在鉴定终止神经母细胞分裂所需基因的筛选,我们鉴定出了Notch和Notch信号通路成分。当Notch被敲低时,神经母细胞会更长时间地维持早期时间因子的表达,延迟晚期时间因子的表达,并持续分裂至成年期。我们发现,在皮层神经胶质细胞、神经母细胞以及分裂后的它们的GMC后代中表达的Delta调节神经母细胞的Notch活性。我们还发现,神经母细胞中的Delta在早期高表达,晚期低表达,并且受内在时间程序控制:早期因子Imp促进Delta表达,晚期因子Syp/E93降低Delta表达。因此,除了全身性类固醇激素信号外,神经母细胞向前的谱系进展还受神经母细胞与其皮层神经胶质细胞/GMC邻居之间的局部细胞间信号传导控制:Delta激活神经母细胞中的Notch,从而结束早期时间程序和早期时间因子的表达。