Cinar Hulusi, Keles Sunduz, Jin Yishi
Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064 USA.
Curr Biol. 2005 Feb 22;15(4):340-6. doi: 10.1016/j.cub.2005.02.025.
Neurons constitute the most diverse cell types and acquire their identity by the activity of particular genetic programs . The GABAergic nervous system in C. elegans consists of 26 neurons that fall into six classes . Animals that are defective in GABAergic neuron function and development display "shrinker" movement , abnormal foraging and defecation . Among the known shrinker genes, unc-25 and unc-47 encode the GABA biosynthetic enzyme glutamic acid decarboxylase and vesicular transporter, respectively . unc-30 encodes a homeodomain protein of the Pitx family and regulates the differentiation of the D-type GABAergic neurons . unc-46 probably functions in presynaptic GABA release , but its identity has not been reported. By cell-based microarray analysis, we identified over 250 genes with enriched expression in GABAergic neurons. The highly enriched gene set included all known genes. In vivo expression study with computational predictions further identified six new genes that are potential transcriptional targets of UNC-30. Behavioral studies of a deletion mutant implicate a function of a nicotinic receptor subunit in D-type neurons. Our analysis demonstrates the utility of neuron-specific genomics in identifying cell-specific genes and regulatory networks.
神经元构成了最多样化的细胞类型,并通过特定基因程序的活动获得其特性。秀丽隐杆线虫中的GABA能神经系统由26个神经元组成,分为六类。GABA能神经元功能和发育有缺陷的动物表现出“收缩”运动、异常觅食和排便。在已知的收缩基因中,unc-25和unc-47分别编码GABA生物合成酶谷氨酸脱羧酶和囊泡转运体。unc-30编码Pitx家族的一个同源结构域蛋白,并调节D型GABA能神经元的分化。unc-46可能在突触前GABA释放中起作用,但其身份尚未报道。通过基于细胞的微阵列分析,我们鉴定出250多个在GABA能神经元中表达丰富的基因。高度富集的基因集包括所有已知基因。结合计算预测的体内表达研究进一步鉴定出六个新基因,它们是UNC-30潜在的转录靶点。一个缺失突变体的行为研究表明,烟碱样受体亚基在D型神经元中有功能。我们的分析证明了神经元特异性基因组学在识别细胞特异性基因和调控网络方面的实用性。