Generation of Multiple Classes of V0 Neurons in Zebrafish Spinal Cord: Progenitor Heterogeneity and Temporal Control of Neuronal Diversity
Generation of Multiple Classes of V0 Neurons in Zebrafish Spinal Cord: Progenitor Heterogeneity and Temporal Control of Neuronal Diversity
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DOI：
10.1523/jneurosci.5500-11.2012
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发表时间：
2012-02-01
影响因子：
5.3
通讯作者：
Higashijima, Shin-ichi
中科院分区：
文献类型：
--
作者：
Satou, Chie;Kimura, Yukiko;Higashijima, Shin-ichi
发育中的脊髓被细分为不同的祖细胞域，每个祖细胞域产生不同类型的神经元。然而，负责在一个区域内产生神经元多样性的发育机制还没有被很好地理解。在这里，我们研究了斑马鱼V0神经元，这些神经元来自P0前体结构域，以解决这个问题。我们发现，所有的V0神经元都有连合轴突，但它们可分为兴奋性和抑制性两类。V0兴奋性神经元(V0-e)根据其轴突轨迹可进一步分为三类：V0-EA(上升)、V0-EB(分叉)和V0-ED(下降)神经元。通过对P0祖细胞及其子代的时间推移成像，我们发现抑制性神经元和兴奋性神经元来自不同的祖细胞。我们还证明了V0-EA神经元是由不同的祖细胞产生的，而V0-EB和V0-ED神经元是由共同的祖先产生的。然后，我们使用出生日期分析来揭示V0-EA、V0-EB和V0-ED神经元是按顺序出现的。通过干扰Notch信号和加速神经元分化，我们可以预见地改变早期出生的V0-e神经元的生成，而代价是较晚出生的神经元。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：来自不同的P0前体细胞和来自相同的P0前体细胞，但以时间依赖的方式产生。
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.