The HMX/NKX homeodomain protein MLS-2 specifies the identity of the AWC sensory neuron type via regulation of the ceh-36 Otx gene in C. elegans
The HMX/NKX homeodomain protein MLS-2 specifies the identity of the AWC sensory neuron type via regulation of the ceh-36 Otx gene in C. elegans
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DOI：
10.1242/dev.044719
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发表时间：
2010-03-15
期刊：
影响因子：
4.6
通讯作者：
Sengupta, Piali
中科院分区：
文献类型：
--
作者：
Kim, Kyuhyung;Kim, Rinho;Sengupta, Piali
有丝分裂后神经元的分化特征是由特定转录因子的表达决定的。调控这些因子的精确时空表达模式的机制还知之甚少。在线虫中，CEH-36OTX Homeobox基因在胚胎后发育的AWC感觉神经元中表达，并调节该神经元亚型的末端分化。在这里，我们证明了HMX/NKX同源结构域蛋白MLS-2调节CEH-36在AWC神经元中的特异性表达。因此，在MLS-2突变体中，AWC神经元不能表达神经元类型特异性特征。MLS-2在有丝分裂后AWC神经元中瞬时表达，并直接启动CEH-36的表达。CEH-36随后与其顺式调控序列中的一个不同位置相互作用，以维持其自身的表达，并直接调节AWC特异性末端分化基因的表达。我们还表明，MLS-2在其他类型的神经元中发挥作用，调节它们的发育和分化。我们的分析描述了一个转录因子级联，它定义了感觉神经元亚型独特的有丝分裂后特征，并提供了对在感觉神经系统中产生功能多样性的时空调节机制的见解。
The differentiated features of postmitotic neurons are dictated by the expression of specific transcription factors. The mechanisms by which the precise spatiotemporal expression patterns of these factors are regulated are poorly understood. In C. elegans, the ceh-36 Otx homeobox gene is expressed in the AWC sensory neurons throughout postembryonic development, and regulates terminal differentiation of this neuronal subtype. Here, we show that the HMX/NKX homeodomain protein MLS-2 regulates ceh-36 expression specifically in the AWC neurons. Consequently, the AWC neurons fail to express neuron type-specific characteristics in mls-2 mutants. mls-2 is expressed transiently in postmitotic AWC neurons, and directly initiates ceh-36 expression. CEH-36 subsequently interacts with a distinct site in its cis-regulatory sequences to maintain its own expression, and also directly regulates the expression of AWC-specific terminal differentiation genes. We also show that MLS-2 acts in additional neuron types to regulate their development and differentiation. Our analysis describes a transcription factor cascade that defines the unique postmitotic characteristics of a sensory neuron subtype, and provides insights into the spatiotemporal regulatory mechanisms that generate functional diversity in the sensory nervous system.