Regulation of Neurogenesis by FGF Signaling and Neurogenin in the Invertebrate ChordateCiona
Regulation of Neurogenesis by FGF Signaling and Neurogenin in the Invertebrate ChordateCiona
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DOI：
10.3389/fcell.2020.00477
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发表时间：
2020-06-23
影响因子：
5.5
通讯作者：
Stolfi, Alberto
中科院分区：
文献类型：
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作者：
Kim, Kwantae;Gibboney, Susanne;Stolfi, Alberto
神经发生是由保守效应物的协同表达驱动的一系列复杂的细胞过程和行为。玻璃海鞘（Ciona）的双极尾神经元（BTNs）按照一个高度动态但又高度定型的发育程序发育，因此可作为神经发生的一个易于研究的模型系统，包括潜在的细胞行为，如神经元分层、迁移和极化轴突生长。在此，我们研究了通过对保守的神经原性因子Neurog进行时空调节来塑造BTN神经发生的上游事件，以及在Neurog活性下游分化的BTN的基因表达谱。我们表明，尽管早期成纤维细胞生长因子（FGF）信号对于Neurog的表达和BTN的特化是必需的，但Fgf8/17/18在后期在尾尖细胞中表达，并抑制前BTN（aBTN）谱系中Neurog的持续表达，使得只有一个细胞（离Fgf8/17/18来源最远的那个细胞）维持Neurog的表达并成为神经元。奇怪的是，Fgf8/17/18可能不影响后BTN（pBTN）的神经发生，而后BTN与表达Fgf8/17/18的细胞直接接触。最后，为了分析与BTN神经发生相关的基因表达，我们对分离的BTN谱系细胞进行了RNA测序，其中通过干扰Neurog的功能增强或抑制了BTN神经发生。这使我们能够鉴定出几个可能在其他动物（包括哺乳动物）的神经发生和神经元迁移中发挥保守作用的候选基因。
Neurogenesis is a complex sequence of cellular processes and behaviors driven by the coordinated expression of conserved effectors. The bipolar tail neurons (BTNs) ofCionadevelop according to a highly dynamic, yet highly stereotyped developmental program and thus could serve as an accessible model system for neurogenesis, including underlying cell behaviors like neuronal delamination, migration, and polarized axon outgrowth. Here we investigate both the upstream events that shape BTN neurogenesis through spatiotemporal regulation of the conserved proneural factor Neurog, spatiotemporal, and the gene expression profile of differentiating BTNs downstream of Neurog activity. We show that, although early FGF signaling is required forNeurogexpression and BTN specification,Fgf8/17/18is expressed in tail tip cells at later stages and suppresses sustainedNeurogexpression in the anterior BTN (aBTN) lineage, such that only one cell (the one furthest from the source of Fgf8/17/18) maintainsNeurogexpression and becomes a neuron. Curiously,Fgf8/17/18might not affect neurogenesis of the posterior BTNs (pBTNs), which are in direct contact with theFgf8/17/18-expressing cells. Finally, to profile gene expression associated with BTN neurogenesis we performed RNAseq of isolated BTN lineage cells in which BTN neurogenesis was enhanced or suppressed by perturbing Neurog function. This allowed us to identify several candidate genes that might play conserved roles in neurogenesis and neuronal migration in other animals, including mammals.