A network approach to analyze neuronal lineage and layer innervation in the Drosophila optic lobes
A network approach to analyze neuronal lineage and layer innervation in the Drosophila optic lobes
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DOI：
10.1371/journal.pone.0227897
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发表时间：
2020-02-05
期刊：
影响因子：
3.7
通讯作者：
Portillo, Jose R.
中科院分区：
文献类型：
--
作者：
del Valle Rodriguez, Alberto;Cera, Martin;Portillo, Jose R.
果蝇（Drosophila melanogaster）的视叶形成了一个高度有线的神经网络，由80多种不同类型的大约130，000个神经元组成。神经元的多样性是如何从非常少的祖细胞中产生的，这是发育神经生物学的一个中心问题。我们使用果蝇的视叶作为范例来理解神经干细胞是如何产生多种神经元类型的。虽然苍蝇脑的发育一直是广泛研究的主题，但对形成成体视叶的细胞类型的谱系关系知之甚少。在这里，我们使用图论进行大规模谱系生物信息学分析。我们产生了大量的细胞克隆，这些细胞克隆在遗传上标记了成神经细胞的后代，并建立了一个数据库来绘制显示细胞类型之间谱系关系的图表。通过建立衡量神经元关系强度的生物学标准和应用社区检测工具，我们已经确定了八个神经元簇。每一簇都包含不同的细胞类型，我们认为它们是八种不同类型的神经母细胞的产物。其中三个聚类与可用的谱系数据相匹配，支持分析的预测价值。最后，我们表明，神经细胞的神经元后代没有优先的神经支配模式，而是成为不同的层和神经髓鞘的一部分。在这里，我们建立了一种新的方法，有助于理解果蝇大脑发育的逻辑，并可应用于更复杂的脊椎动物的大脑。
The optic lobes of the fruit fly Drosophila melanogaster form a highly wired neural network composed of roughly 130.000 neurons of more than 80 different types. How neuronal diversity arises from very few cell progenitors is a central question in developmental neurobiology. We use the optic lobe of the fruit fly as a paradigm to understand how neuroblasts, the neural stem cells, generate multiple neuron types. Although the development of the fly brain has been the subject of extensive research, very little is known about the lineage relationships of the cell types forming the adult optic lobes. Here we perform a large-scale lineage bioinformatics analysis using the graph theory. We generated a large collection of cell clones that genetically label the progeny of neuroblasts and built a database to draw graphs showing the lineage relationships between cell types. By establishing biological criteria that measures the strength of the neuronal relationships and applying community detection tools we have identified eight clusters of neurons. Each cluster contains different cell types that we pose are the product of eight distinct classes of neuroblasts. Three of these clusters match the available lineage data, supporting the predictive value of the analysis. Finally, we show that the neuronal progeny of a neuroblast do not have preferential innervation patterns, but instead become part of different layers and neuropils. Here we establish a new methodology that helps understanding the logic of Drosophila brain development and can be applied to the more complex vertebrate brains.