大脑由有限数量的神经干细胞产生的不同神经元组成。果蝇神经干细胞称为神经母细胞(NBs),根据它们在大脑中的位置,产生各种谱系大小的特定神经谱系。在果蝇视觉处理中心-视神经叶(Ols),源自神经上皮(NE)的髓质NBs产生髓质皮质的神经元和神经胶质细胞。到目前为止,髓质NB停止的时机和机制尚不清楚。在这项研究中,我们表明,早期p发育过程中髓质NBs的终止取决于NE干细胞池的耗尽。因此,在幼虫神经发生过程中改变NE-NB过渡会破坏髓质NB的及时终止。髓质NBs通过凋亡的组合终止神经发生,通过Prospero进行终端对称划分,通过胶质细胞缺失(Gcm)转变为胶质细胞生成,然而,这些过程彼此独立地发生。我们还表明,延髓NBs的时间进展大多不需要它们的终止。由于果蝇OL与哺乳动物神经发生具有相似的分裂模式,了解这些祖细胞在发育过程中何时以及如何停止增殖,对于哺乳动物大脑大小的确定和其整体功能的调节具有重要意义。
The brain is consisted of diverse neurons arising from a limited number of neural stem cells. Drosophila neural stem cells called neuroblasts (NBs) produces specific neural lineages of various lineage sizes depending on their location in the brain. In the Drosophila visual processing centre - the optic lobes (OLs), medulla NBs derived from the neuroepithelium (NE) give rise to neurons and glia cells of the medulla cortex. The timing and the mechanisms responsible for the cessation of medulla NBs are so far not known. In this study, we show that the termination of medulla NBs during early pupal development is determined by the exhaustion of the NE stem cell pool. Hence, altering NE-NB transition during larval neurogenesis disrupts the timely termination of medulla NBs. Medulla NBs terminate neurogenesis via a combination of apoptosis, terminal symmetric division via Prospero, and a switch to gliogenesis via Glial Cell Missing (Gcm); however, these processes occur independently of each other. We also show that temporal progression of the medulla NBs is mostly not required for their termination. As the Drosophila OL shares a similar mode of division with mammalian neurogenesis, understanding when and how these progenitors cease proliferation during development can have important implications for mammalian brain size determination and regulation of its overall function.
Every cell in the body can be traced back to a stem cell. For instance, most cells in the adult brains of fruit flies come from a type of stem cell known as a neuroblast. This includes neurons and glial cells (which support and protect neurons) in the optic lobe, the part of the brain that processes visual information. The numbers of neurons and glia in the optic lobe are tightly regulated such that when the right numbers are reached, the neuroblasts stop making more and are terminated. But how and when this occurs is poorly understood. To investigate, Nguyen and Cheng studied when neuroblasts disappear in the optic lobe over the course of development. This revealed that the number of neuroblasts dropped drastically 12 to 18 hours after the fruit fly larvae developed in to pupae, and were completely gone by 30 hours in to pupae life. Further experiments revealed that the timing of this decrease is influenced by neuroepithelium cells, the pool of stem cells that generate neuroblasts during the early stages of development. Nguyen and Cheng found that speeding up this transition so that neuroblasts arise from the neuroepithelium earlier, led neuroblasts to disappear faster from the optic lobe; whereas delaying the transition caused neuroblasts to persist for much longer. Thus, the time at which neuroblasts are born determines when they are terminated. Furthermore, Nguyen and Cheng showed that the neuroblasts were lost through a combination of means. This includes dying via a process called apoptosis, dividing to form two mature neurons, or switching to a glial cell fate. These findings provide a deeper understanding of the mechanisms regulating stem cell pools and their conversion to different cell types, a process that is crucial to the proper development of the brain. How cells divide to form the optic lobe of fruit flies is similar to how new neurons arise in the mammalian brain. Understanding how and when stem cells in the fruit fly brain stop proliferating could therefore provide new insights in to the development of the human brain.