Neural circuitry for mating and reproduction resides within the terminal segments of central nervous system (CNS) which express Hox paralogous group 9-13 (in vertebrates) or Abdominal-B (Abd-B) in Drosophila. Terminal neuroblasts (NBs) in A8-A10 segments of Drosophila larval CNS are subdivided into two groups based on expression of transcription factor Doublesex (Dsx). While the sex specific fate of Dsx-positive NBs is well investigated, the fate of Dsx-negative NBs is not known so far. Our studies with Dsx-negative NBs suggests that these cells, like their abdominal counterparts (in A3-A7 segments) use Hox, Grainyhead (Grh) and Notch to undergo cell death during larval development. This cell death also happens by transcriptionally activating RHG family of apoptotic genes through a common apoptotic enhancer in early to mid L3 stages. However, unlike abdominal NBs (in A3-A7 segments) which use increasing levels of resident Hox factor Abdominal-A (Abd-A) as an apoptosis trigger, Dsx-negative NBs (in A8-A10 segments) keep the levels of resident Hox factor Abd-B constant. These cells instead utilize increasing levels of the temporal transcription factor Grh and a rise in Notch activity to gain apoptotic competence. Biochemical and in vivo analysis suggest that Abdominal-A and Grh binding motifs in the common apoptotic enhancer also function as Abdominal-B and Grh binding motifs and maintains the enhancer activity in A8-A10 NBs. Finally, the deletion of this enhancer by the CRISPR-Cas9 method blocks the apoptosis of Dsx-negative NBs. These results highlight the fact that Hox dependent NB apoptosis in abdominal and terminal regions utilizes common molecular players (Hox, Grh and Notch), but seems to have evolved different molecular strategies to pattern CNS.

中文翻译：

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Notch和Grainyhead的顺序激活使果蝇中枢神经系统中表达Ab的B型幼虫成神经细胞具有凋亡能力。

用于交配和繁殖的神经回路位于中枢神经系统（CNS）的末端，该末端表达果蝇中的Hox旁系9-13组（在脊椎动物中）或Abdominal-B（Abd-B）。根据转录因子Doublesex（Dsx）的表达，将果蝇幼虫CNS的A8-A10区段中的末端神经母细胞（NBs）分为两组。尽管对Dsx阳性NB的性别特定命运进行了充分的调查，但到目前为止，Dsx阴性NB的命运尚不清楚。我们对Dsx阴性NB的研究表明，这些细胞像它们的腹部对应细胞一样（在A3-A7区段中）使用Hox，粒头（Grh）和Notch在幼虫发育期间经历细胞死亡。这种细胞死亡也通过在L3早期至中期通过常见的凋亡增强子转录激活RHG凋亡基因家族而发生。然而，与使用增加的常驻Hox因子Abdominal-A（Abd-A）的腹部NB（在A3-A7段中）作为凋亡的触发因素不同，Dsx阴性NB（在A8-A10段中）保持常驻Hox因子Abd的水平-B常数。这些细胞反而利用增加的时间转录因子Grh水平和Notch活性的升高来获得凋亡能力。生化和体内分析表明，常见凋亡增强子中的Abdominal-A和Grh结合基序还可以充当Abdominal-B和Grh结合基序，并在A8-A10 NB中保持增强子活性。最后，通过CRISPR-Cas9方法删除该增强子可阻断Dsx阴性NBs的凋亡。这些结果突显了一个事实，即腹部和末端区域中依赖Hox的NB细胞凋亡利用了常见的分子分子（Hox，Grh和Notch），