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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Neurogenin1 is a determinant of zebrafish basal forebrain dopaminergic neurons and is regulated by the conserved zinc finger protein Tof/Jezl
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Neurogenin1 is a determinant of zebrafish basal forebrain dopaminergic neurons and is regulated by the conserved zinc finger protein Tof/Jezl

机译：Neurogenin1是斑马鱼基底前脑多巴胺能神经元的决定因素，并受保守的锌指蛋白Tof / Jezl的调节

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摘要

The development of vertebrate basal forebrain dopaminergic (DA) neurons requires the conserved zinc finger protein Too Few (Tof/FezI) in zebrafish. However, how Tof/FezI regulates the commitment and differentiation of these DA neurons is not known. Proneural genes encoding basic helix-loop-helix transcription factors regulate the development of multiple neuronal lineages, but their involvement in vertebrate DA neuron determination is unclear. Here we show that neurogenin 1 (ngn1), a vertebrate proneural gene related to the Drosophila atonal, is expressed in and required for specification of DA progenitor cells, and when overexpressed leads to supernumerary DA neurons in the forebrain of zebrafish. Overexpression of ngn1 is also sufficient to induce tyrosine hydroxylase expression in addition to the panneuronal marker Hu in nonneural ectoderm. We further show that Tof/FezI is required to establish basal forebrain ngn1-expressing DA progenitor domains. These findings identify Ngn1 as a determinant of brain DA neurons and provide insights into how Tof/FezI regulates the development of these clinically important neuronal types.
机译：脊椎动物基底前脑多巴胺能（DA）神经元的发育需要斑马鱼中的锌指蛋白保守（Tof / FezI）太少。但是，Tof / FezI如何调节这些DA神经元的定向和分化尚不清楚。编码基本螺旋-环-螺旋转录因子的proneural基因调节多个神经元谱系的发育，但它们是否参与脊椎动物DA神经元的确定尚不清楚。在这里，我们显示神经原蛋白1（ngn1），与果蝇无声有关的脊椎动物前神经基因，在DA祖细胞的规范中表达并需要，而当过表达时会在斑马鱼的前脑中产生多余的DA神经元。除了在非神经外胚层中泛神经标记物Hu之外，ngn1的过表达还足以诱导酪氨酸羟化酶表达。我们进一步表明，Tof / FezI是建立基础前脑ngn1表达DA祖域所必需的。这些发现确定了Ngn1是大脑DA神经元的决定因素，并为Tof / FezI如何调节这些临床上重要的神经元类型的发育提供了见识。

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