Specification and survival of post-metamorphic branchiomeric neurons in the hindbrain of a non-vertebrate chordate.
Specification and survival of post-metamorphic branchiomeric neurons in the hindbrain of a non-vertebrate chordate.
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非脊椎动物脊索动物后脑变态后鳃节神经元的规格和存活。
DOI：
10.1101/2023.06.16.545305
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Stolfi,Alberto
中科院分区：
文献类型：
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作者：
Gigante,EduardoD;Piekarz,KatarzynaM;Gurgis,Alexandra;Cohen,Leslie;Razy-Krajka,Florian;Popsuj,Sydney;Ali,HussanS;Sundaram,ShruthiMohana;Stolfi,Alberto
被囊动物是脊椎动物的姐妹类群，但大多数物种的生命周期分为游泳的幼虫和静止的成虫阶段。在变态过程中，幼虫神经元大部分被成虫特有的神经元取代。然而，这种神经替代背后的调节机制仍然很大程度上未知。通过在被囊动物 Ciona 中使用组织特异性 CRISPR/Cas9 介导的诱变，我们发现保守的后脑和鳃聚神经元调节因子 Pax2/5/8 和 Phox2 的直系同源物需要指定“颈部”，即在幼虫中留出的细胞区室，以在成虫中产生颅运动神经元样神经元。使用批量和单细胞 RNAseq 分析，我们还表征了 Pax2/5/8 下游 Neck 的转录组。令人惊讶的是，我们发现颈部来源的成体纤毛运动神经元在幼虫中开始分化，这与长期以来认为成体神经系统仅在幼虫神经元在变态过程中定居和死亡后形成的假设相反。最后，我们发现在幼虫阶段操纵 FGF 信号传导会改变颈部及其衍生物的模式。 FGF 的抑制会将颈部细胞转化为无法在变态中存活的幼虫神经元，而延长 FGF 信号转导则会促进成体神经干细胞样的命运。
Tunicates are the sister group to the vertebrates, yet most species have a life cycle split between swimming larva and sedentary adult phases. During metamorphosis, larval neurons are largely replaced by adult-specific ones. Yet the regulatory mechanisms underlying this neural replacement remain largely unknown. Using tissue-specific CRISPR/Cas9-mediated mutagenesis in the tunicate Ciona, we show that orthologs of conserved hindbrain and branchiomeric neuron regulatory factors Pax2/5/8 and Phox2 are required to specify the “Neck”, a compartment of cells set aside in the larva to give rise to cranial motor neuron-like neurons in the adult. Using bulk and single-cell RNAseq analyses, we also characterize the transcriptome of the Neck downstream of Pax2/5/8. Surprisingly, we find that Neck-derived adult ciliomotor neurons begin to differentiate in the larva, contrary to the long-held assumption that the adult nervous system is formed only after settlement and the death of larval neurons during metamorphosis. Finally, we show that manipulating FGF signaling during the larval phase alters the patterning of the Neck and its derivatives. Suppression of FGF converts Neck cells into larval neurons that fail to survive metamorphosis, while prolonged FGF signaling promotes an adult neural stem cell-like fate instead.