A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans.
A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans.
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发表时间：
2001-06
期刊：
影响因子：
4.6
通讯作者：
Zeynep Altun-Gultekin;Y. Andachi;E. Tsalik;D. Pilgrim;Y. Kohara;O. Hobert
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作者：
Zeynep Altun-Gultekin;Y. Andachi;E. Tsalik;D. Pilgrim;Y. Kohara;O. Hobert
神经系统的发育需要多种调节因子的协调活动，这些调节因子定义了特定神经元亚型的个体特性。我们报告了由三种同源域蛋白组成的调控级联，这些蛋白的作用是定义线虫秀丽隐杆线虫中特定中间神经元类别的特性。我们描述了一组 AIY 中间神经元类特征的分化标记，并表明 ceh-10 配对型和 ttx-3 LIM 型同源框基因具有调节 AIY 中间神经元所有已知亚型特异性特征的功能。相比之下，ceh-10和ttx-3突变体中一些泛神经元特征的获得不受影响，这表明这些同源框基因的活性将泛神经元与亚型特异性分化程序分开。 LIM 同源框基因 ttx-3 似乎在 AIY 分化的调节中发挥核心作用。 ttx-3 突变体不仅失去了所有 AIY 亚型特征，而且 ttx-3 的异位错误表达也足以在一组有限的神经元中诱导 AIY 样特征。 ceh-10 和 ttx-3 的靶标之一是一种新型同源框基因，ceh-23。我们表明，ceh-23 并不是 AIY 分化特征的最初采用所必需的，而是维持一种定义的 AIY 分化特征的表达所必需的。最后，我们证明 ceh-10、ttx-3 和 ceh-23 之间的调节关系在神经系统的其他神经元中仅部分保守。我们的研究结果说明了神经系统转录调控的复杂性，并为转录因子作用的复杂相互依赖性提供了一个例子。
The development of the nervous system requires the coordinated activity of a variety of regulatory factors that define the individual properties of specific neuronal subtypes. We report a regulatory cascade composed of three homeodomain proteins that act to define the properties of a specific interneuron class in the nematode C. elegans. We describe a set of differentiation markers characteristic for the AIY interneuron class and show that the ceh-10 paired-type and ttx-3 LIM-type homeobox genes function to regulate all known subtype-specific features of the AIY interneurons. In contrast, the acquisition of several pan-neuronal features is unaffected in ceh-10 and ttx-3 mutants, suggesting that the activity of these homeobox genes separates pan-neuronal from subtype-specific differentiation programs. The LIM homeobox gene ttx-3 appears to play a central role in regulation of AIY differentiation. Not only are all AIY subtype characteristics lost in ttx-3 mutants, but ectopic misexpression of ttx-3 is also sufficient to induce AIY-like features in a restricted set of neurons. One of the targets of ceh-10 and ttx-3 is a novel type of homeobox gene, ceh-23. We show that ceh-23 is not required for the initial adoption of AIY differentiation characteristics, but instead is required to maintain the expression of one defined AIY differentiation feature. Finally, we demonstrate that the regulatory relationship between ceh-10, ttx-3 and ceh-23 is only partially conserved in other neurons in the nervous system. Our findings illustrate the complexity of transcriptional regulation in the nervous system and provide an example for the intricate interdependence of transcription factor action.