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Generation of Multiple Classes of V0 Neurons in Zebrafish Spinal Cord : Progenitor Heterogeneity and Temporal Control of Neuronal Diversity

斑马鱼脊髓中多类 V0 神经元的产生：祖细胞异质性和神经元多样性的时间控制

基本信息

批准号：
23700409
负责人：
SATO Chie
金额：
$ 2.83万
依托单位：
大学共同利用機関法人自然科学研究機構(岡崎共通研究施設) (2012-2013)National Institutes of Natural Sciences Okazaki Research Facilities (2011)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2011
资助国家：
日本
起止时间：
2011 至 2013
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23700409/
关键词：
ゼブラフィッシュ神経前駆体脊髄

项目摘要

The developing spinal cord is subdivided into distinct progenitor domains, each of which gives rise to different types of neurons. However, the developmental mechanisms responsible for generating neuronal diversity within a domain are not well understood. Here, we have studied zebrafish V0 neurons, those that derive from the p0 progenitor domain, to address this question. We find that all V0 neurons have commissural axons, but they can be divided into excitatory and inhibitory classes. V0 excitatory neurons (V0-e) can be further categorized into three groups based on their axonal trajectories; V0-eA (ascending), V0-eB (bifurcating), and V0-eD (descending) neurons. By using time-lapse imaging of p0 progenitors and their progeny, we show that inhibitory and excitatory neurons are produced from different progenitors. We also demonstrate that V0-eA neurons are produced from distinct progenitors, while V0-eB and V0-eD neurons are produced from common progenitors. We then use birth-date analysis to reveal that V0-eA, V0-eB, and V0-eD neurons arise in this order. By perturbing Notch signaling and accelerating neuronal differentiation, we predictably alter the generation of early born V0-e neurons at the expense of later born ones. These results suggest that multiple types of V0 neurons are produced by two distinct mechanisms; from heterogeneous p0 progenitors and from the same p0 progenitor, but in a time-dependent manner.

发育中的脊髓被细分为不同的祖细胞区域，每个区域产生不同类型的神经元。然而，负责产生神经元的多样性在一个域的发展机制还没有得到很好的理解。在这里，我们研究了斑马鱼V0神经元，那些来自p0祖域，以解决这个问题。我们发现，所有的V0神经元连合轴突，但他们可以分为兴奋和抑制类。V0兴奋性神经元（V0-e）可以根据其轴突轨迹进一步分为三组：V0-eA（上行）、V0-eB（分叉）和V0-艾德（下行）神经元。通过使用p0祖细胞及其后代的延时成像，我们表明抑制性和兴奋性神经元是由不同的祖细胞产生的。我们还表明，V0-eA神经元产生的不同的祖细胞，而V0-eB和V0-艾德神经元产生的共同的祖细胞。然后，我们使用出生日期分析，以揭示V0-eA，V0-eB和V0-艾德神经元出现在这个顺序。通过干扰Notch信号传导和加速神经元分化，我们可以预见地改变了早期出生的V0-e神经元的产生，而牺牲了后来出生的神经元。这些结果表明，多种类型的V0神经元是由两种不同的机制产生的;从异质性P0祖细胞和从相同的P0祖细胞，但在一个时间依赖性的方式。