Delta-dependent Notch activation closes the early neuroblast temporal program to promote lineage progression and neurogenesis termination in Drosophila.
Delta-dependent Notch activation closes the early neuroblast temporal program to promote lineage progression and neurogenesis termination in Drosophila.
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Delta依赖性Notch激活关闭早期神经母细胞时间程序，促进果蝇谱系进展和神经发生终止。
DOI：
10.1101/2023.03.28.534626
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Siegrist,SarahE
中科院分区：
文献类型：
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作者：
Sood,Chhavi;Nahid,MdAusrafuggaman;Branham,KendallR;Pahl,MatthewC;Doyle,SusanE;Siegrist,SarahE
果蝇中的神经母细胞不对称分裂，顺序表达一系列内在因子以产生多种神经元类型。这些被称为时间因素的内在因素决定了神经母细胞响应类固醇激素信号的转变时间，并指定了神经母细胞神经元后代的早期与晚期时间命运。在完成它们的时间程序后，成神经细胞分化或死亡，最终确定每个成神经细胞谱系中的神经元数量和类型。从一个旨在鉴定终止成神经细胞分裂所需基因的筛选中，我们鉴定了Notch和Notch途径组分。当Notch被敲除时，成神经细胞维持早期时间因子表达的时间更长，延迟晚期时间因子表达，并继续分裂到成年期。我们发现，Delta，表达在皮质胶质细胞，神经母细胞，分裂后，他们的GMC后代，调节神经母细胞Notch活性。我们还发现Delta在神经母细胞中表达早高晚低，并且受内在时间程序控制：早期因子Imp促进Delta，晚期因子Syp/E93降低Delta。因此，除了全身性类固醇激素的线索，正向谱系进展是由神经母细胞和他们的皮质神经胶质细胞/GMC邻居之间的局部细胞-细胞信号传导控制的：Delta反式激活神经母细胞中的Notch，使早期的时间程序和早期的时间因子表达结束。
Neuroblasts in Drosophila 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.