Curriculum in Neurobiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.
Development. 2011 Jun;138(11):2171-83. doi: 10.1242/dev.056507.
Dopaminergic neurons play important behavioral roles in locomotion, reward and aggression. The Drosophila H-cell is a dopaminergic neuron that resides at the midline of the ventral nerve cord. Both the H-cell and the glutamatergic H-cell sib are the asymmetric progeny of the MP3 midline precursor cell. H-cell sib cell fate is dependent on Notch signaling, whereas H-cell fate is Notch independent. Genetic analysis of genes that could potentially regulate H-cell fate revealed that the lethal of scute [l(1)sc], tailup and SoxNeuro transcription factor genes act together to control H-cell gene expression. The l(1)sc bHLH gene is required for all H-cell-specific gene transcription, whereas tailup acts in parallel to l(1)sc and controls genes involved in dopamine metabolism. SoxNeuro functions downstream of l(1)sc and controls expression of a peptide neurotransmitter receptor gene. The role of l(1)sc may be more widespread, as a l(1)sc mutant shows reductions in gene expression in non-midline dopaminergic neurons. In addition, l(1)sc mutant embryos possess defects in the formation of MP4-6 midline precursor and the median neuroblast stem cell, revealing a proneural role for l(1)sc in midline cells. The Notch-dependent progeny of MP4-6 are the mVUM motoneurons, and these cells also require l(1)sc for mVUM-specific gene expression. Thus, l(1)sc plays an important regulatory role in both neurogenesis and specifying dopaminergic neuron and motoneuron identities.
多巴胺能神经元在运动、奖励和攻击等行为中发挥重要作用。果蝇 H 细胞是一种位于腹神经索中线的多巴胺能神经元。H 细胞和谷氨酸能 H 细胞 sib 都是 MP3 中线前体细胞的不对称后代。H 细胞 sib 的命运依赖于 Notch 信号，而 H 细胞的命运则与 Notch 无关。对可能调节 H 细胞命运的基因进行遗传分析表明， lethal of scute [l(1)sc]、tailup 和 SoxNeuro 转录因子基因共同作用，控制 H 细胞基因表达。l(1)sc bHLH 基因是所有 H 细胞特异性基因转录所必需的，而 tailup 与 l(1)sc 平行作用，并控制参与多巴胺代谢的基因。SoxNeuro 作用于 l(1)sc 的下游，控制肽能神经递质受体基因的表达。l(1)sc 的作用可能更为广泛，因为 l(1)sc 突变体显示非中线多巴胺能神经元中的基因表达减少。此外，l(1)sc 突变体胚胎中 MP4-6 中线前体细胞和中脑神经干细胞形成缺陷，表明 l(1)sc 在中线细胞中具有神经前体细胞的作用。MP4-6 的 Notch 依赖性后代是 mVUM 运动神经元，这些细胞也需要 l(1)sc 来表达 mVUM 特异性基因。因此，l(1)sc 在神经发生和指定多巴胺能神经元和运动神经元身份方面发挥着重要的调节作用。
