Etchberger John F, Lorch Adam, Sleumer Monica C, Zapf Richard, Jones Steven J, Marra Marco A, Holt Robert A, Moerman Donald G, Hobert Oliver
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032, USA.
Genes Dev. 2007 Jul 1;21(13):1653-74. doi: 10.1101/gad.1560107.
Taste receptor cells constitute a highly specialized cell type that perceives and conveys specific sensory information to the brain. The detailed molecular composition of these cells and the mechanisms that program their fate are, in general, poorly understood. We have generated serial analysis of gene expression (SAGE) libraries from two distinct populations of single, isolated sensory neuron classes, the gustatory neuron class ASE and the thermosensory neuron class AFD, from the nematode Caenorhabditis elegans. By comparing these two libraries, we have identified >1000 genes that define the ASE gustatory neuron class on a molecular level. This set of genes contains determinants of the differentiated state of the ASE neuron, such as a surprisingly complex repertoire of transcription factors (TFs), ion channels, neurotransmitters, and receptors, as well as seven-transmembrane receptor (7TMR)-type putative gustatory receptor genes. Through the in vivo dissection of the cis-regulatory regions of several ASE-expressed genes, we identified a small cis-regulatory motif, the "ASE motif," that is required for the expression of many ASE-expressed genes. We demonstrate that the ASE motif is a binding site for the C2H2 zinc finger TF CHE-1, which is essential for the correct differentiation of the ASE gustatory neuron. Taken together, our results provide a unique view of the molecular landscape of a single neuron type and reveal an important aspect of the regulatory logic for gustatory neuron specification in C. elegans.
味觉受体细胞构成了一种高度特化的细胞类型,它能感知并向大脑传递特定的感官信息。总体而言,这些细胞的详细分子组成以及决定其命运的机制还知之甚少。我们从线虫秀丽隐杆线虫的两种不同的单个分离感觉神经元类别,即味觉神经元类别 ASE 和热敏神经元类别 AFD 中生成了基因表达序列分析(SAGE)文库。通过比较这两个文库,我们在分子水平上鉴定出了 >1000 个定义 ASE 味觉神经元类别的基因。这组基因包含 ASE 神经元分化状态的决定因素,例如转录因子(TFs)、离子通道、神经递质和受体的惊人复杂组合,以及七跨膜受体(7TMR)型假定味觉受体基因。通过对几个 ASE 表达基因的顺式调控区域进行体内剖析,我们鉴定出了一个小的顺式调控基序,即“ASE 基序”,它是许多 ASE 表达基因表达所必需的。我们证明 ASE 基序是 C2H2 锌指 TF CHE-1 的结合位点,这对于 ASE 味觉神经元的正确分化至关重要。综上所述,我们的结果提供了对单一神经元类型分子景观的独特视角,并揭示了秀丽隐杆线虫味觉神经元特化调控逻辑的一个重要方面。