Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
Development. 2010 Mar;137(6):963-74. doi: 10.1242/dev.044719. Epub 2010 Feb 11.
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.
后分化神经元的特征由特定转录因子的表达决定。这些因子精确的时空表达模式是如何被调控的，目前还知之甚少。在秀丽隐杆线虫中，ceh-36 Otx 同源盒基因在整个胚胎后发育过程中都在 AWC 感觉神经元中表达，并调节该神经元亚型的终末分化。在这里，我们表明 HMX/NKX 同源域蛋白 MLS-2 特异性地调控 AWC 神经元中的 ceh-36 表达。因此，在 mls-2 突变体中，AWC 神经元无法表达神经元类型特异性特征。mls-2 在有丝分裂后的 AWC 神经元中短暂表达，并直接启动 ceh-36 的表达。CEH-36 随后与顺式调控序列中的独特位点相互作用，以维持其自身的表达，并且还直接调控 AWC 特异性终末分化基因的表达。我们还表明，MLS-2 在其他神经元类型中发挥作用，以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反应，该反应定义了感觉神经元亚型的独特后分化特征，并提供了对感觉神经系统中产生功能多样性的时空调控机制的深入了解。
