Neurogenin1 is a determinant of zebrafish basal forebrain dopaminergic neurons and is regulated by the conserved zinc finger protein Tof/Jezl
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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DOI：
10.1073/pnas.0600337103
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发表时间：
2006-03-28
影响因子：
11.1
通讯作者：
Guo, S
中科院分区：
文献类型：
--
作者：
Jeong, JY;Einhorn, Z;Guo, S
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保守的锌指蛋白Too Few（Tof/FezI）。然而，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-螺旋转录因子的原神经基因调节多种神经元谱系的发育，但它们参与脊椎动物DA神经元的决定尚不清楚。在这里，我们表明，neurogenin 1（ngn 1），脊椎动物proneural基因相关的果蝇无调，表达和所需的规格的DA祖细胞，当过表达导致多余的DA神经元在前脑的斑马鱼。ngn 1的过表达也足以诱导酪氨酸羟化酶的表达，除了泛神经元标记胡在非神经外胚层。我们进一步表明，Tof/FezI需要建立基底前脑ngn 1表达DA祖域。这些发现将Ngn 1确定为大脑DA神经元的决定因素，并为Tof/FezI如何调节这些临床重要神经元类型的发育提供了见解。
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.