Current Biology ( IF 8.1 ) Pub Date : 2022-12-19 , DOI: 10.1016/j.cub.2022.11.043
Megan R Radler 1 , Xiaonan Liu 2 , Megan Peng 1 , Brenna Doyle 1 , Kazuhito Toyo-Oka 2 , Elias T Spiliotis 1
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Pyramidal neurons are a major cell type of the forebrain, consisting of a pyramidally shaped soma with axonal and apicobasal dendritic processes. It is poorly understood how the neuronal soma develops its pyramidal morphology, while generating neurites of the proper shape and orientation. Here, we discovered that the spherical somata of immature neurite-less neurons possess a circumferential wreath-like network of septin filaments, which promotes neuritogenesis by balancing the protrusive activity of lamellipodia and filopodia. In embryonic rat hippocampal and mouse cortical neurons, the septin wreath network consists of curvilinear filaments that contain septins 5, 7, and 11 (Sept5/7/11). The Sept5/7/11 wreath network demarcates a zone of myosin II enrichment and Arp2/3 diminution at the base of filopodial actin bundles. In Sept7-depleted neurons, cell bodies are enlarged with hyperextended lamellae and abnormally shaped neurites that originate from lamellipodia. This phenotype is accompanied by diminished myosin II and filopodia lifetimes and increased Arp2/3 and lamellipodial activity. Inhibition of Arp2/3 rescues soma and neurite phenotypes, indicating that the septin wreath network suppresses the extension of lamellipodia, facilitating the formation of neurites from the filopodia of a consolidated soma. We show that this septin function is critical for developing a pyramidally shaped soma with properly distributed and oriented dendrites in cultured rat hippocampal neurons and in vivo in mouse perinatal cortical neurons. Therefore, the somatic septin cytoskeleton provides a key morphogenetic mechanism for neuritogenesis and the development of pyramidal neurons.
中文翻译:
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锥体神经元形态发生需要一个隔膜网络来稳定丝状伪足并在神经突起始过程中抑制片状伪足
锥体神经元是前脑的主要细胞类型,由具有轴突和顶端树突的锥体形体组成。人们对神经元胞体如何发展其锥体形态,同时产生适当形状和方向的神经突的了解知之甚少。在这里,我们发现未成熟的无神经突神经元的球形体细胞具有环形花圈状隔膜丝网络,它通过平衡板状伪足和丝状伪足的突出活动来促进神经突发生。在胚胎大鼠海马和小鼠皮质神经元中,septin 花环网络由包含 septin 5、7 和 11 的曲线细丝组成(2011 年 9 月 7 日)。 2011 年 9 月 7 日的花环网络在丝状肌动蛋白束底部划定了肌球蛋白 II 富集区和 Arp2/3 减少区。在 Sept7 耗尽的神经元中,细胞体增大,片层过度伸展,并且源自片状伪足的形状异常的神经突。这种表型伴随着肌球蛋白 II 和丝状伪足寿命的缩短以及 Arp2/3 和板状伪足活性的增加。抑制 Arp2/3 可挽救体细胞和神经突表型,表明隔膜环网络抑制板状伪足的延伸,促进从巩固体细胞的丝状伪足形成神经突。我们表明,这种隔膜功能对于在培养的大鼠海马神经元和体内的小鼠围产期皮质神经元中发育具有正确分布和定向的树突的金字塔形体体至关重要。因此,体细胞脓毒症细胞骨架为神经突发生和锥体神经元的发育提供了关键的形态发生机制。