A transcriptional regulatory cascade that controls left/right asymmetry in chemosensory neurons of C-elegans
A transcriptional regulatory cascade that controls left/right asymmetry in chemosensory neurons of C-elegans
复制标题
DOI：
10.1101/gad.1117903
复制
发表时间：
2003-09-01
影响因子：
10.5
通讯作者：
Hobert, O
中科院分区：
文献类型：
--
作者：
Chang, S;Johnston, RJ;Hobert, O
人们对神经系统中左/右（L/R）轴差异模式形成的分子机制知之甚少。线虫秀丽隐杆线虫的神经系统显示出 L/R 不对称的几个例子，包括两个 ASE 味觉受体神经元（ASE 左 (ASEL) 和 ASE 右 (ASER)）显示的方向不对称。尽管根据所有已知的形态学标准是双侧对称的，但这两个神经元表现出不同的化学感觉能力，与三个假定的感觉受体基因（仅在 ASER 中表达的 gcy-5、仅在 ASEL 中表达的 gcy-6 和 gcy-7）的 L/R 不对称表达相关。为了了解 L/R 不对称建立的遗传基础，我们筛选了不对称 gcy 基因表达模式被破坏的突变体，并鉴定了一系列对称和不对称表达的转录因子，这些转录因子是顺序限制 gcy 基因表达到左侧或右侧 ASE 细胞所必需的。这些因子包括锌指转录因子 che-1；同源盒基因 cog-1、ceh-36 和 lim-6；以及转录辅助因子 unc-37/Groucho 和 lin-49。这种调节层次的具体特征是依次作用的抑制性相互作用以及对抗积极和消极调节因素的精细平衡活动。不对称的一个关键触发因素是 Nkx6 型 COG-1 同源域蛋白的 L/R 差异表达。因此，我们的研究鉴定了假定的 L/R 不对称信号事件的转录介质，并表明这些蛋白质的脊椎动物同源物在调节脊椎动物大脑不对称性方面可能具有相似的功能。
The molecular mechanisms of differential pattern formation along the left/right (L/R) axis in the nervous system are poorly understood. The nervous system of the nematode Caenorhabditis elegans displays several examples of L/R asymmetry, including the directional asymmetry displayed by the two ASE taste receptor neurons, ASE left (ASEL) and ASE right (ASER). Although bilaterally symmetric in regard to all known morphological criteria, these two neurons display distinct chemosensory capacities that correlate with the L/R asymmetric expression of three putative sensory receptor genes, gcy-5, expressed only in ASER, and gcy-6 and gcy-7, expressed only in ASEL. In order to understand the genetic basis of L/R asymmetry establishment, we screened for mutants in which patterns of asymmetric gcy gene expression are disrupted, and we identified a cascade of several symmetrically and asymmetrically expressed transcription factors that are sequentially required to restrict gcy gene expression to either the left or right ASE cell. These factors include the zinc finger transcription factor che-1; the homeobox genes cog-1, ceh-36, and lim-6; and the transcriptional cofactors unc-37/Groucho and lin-49. Specific features of this regulatory hierarchy are sequentially acting repressive interactions and the finely balanced activity of antagonizing positive and negative regulatory factors. A key trigger for asymmetry is the L/R differential expression of the Nkx6-type COG-1 homeodomain protein. Our studies have thus identified transcriptional mediators of a putative L/R-asymmetric signaling event and suggest that vertebrate homologs of these proteins may have similar functions in regulating vertebrate brain asymmetries.