Fernandez Robert W, Digirolamo Angelo J, Valperga Giulio, Aguilar G Robert, Molina-García Laura, Kersh Rinn M, Wang Chen, Pe Karinna, Ramadan Yasmin H, Loer Curtis, Barrios Arantza, Hobert Oliver
Department of Biological Sciences, Columbia University, Howard Hughes Medical Institute, 1212 Amsterdam Avenue, New York, NY 10025, USA.
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
bioRxiv. 2025 May 17:2025.05.13.653874. doi: 10.1101/2025.05.13.653874.
We explore here how neuronal cell type diversity is genetically delineated in the context of the large, but poorly studied male-specific nervous system of the nematode Mostly during postembryonic development, the male adds 93 male-specific neurons, falling into 25 cardinal classes, to the predominantly embryonically generated, sex-shared nervous system, comprised of 294 neurons (116 cardinal classes). Using engineered reporter alleles, we investigate here the expression pattern of 40 phylogenetically conserved homeodomain proteins within the male-specific nervous system of demonstrating that in aggregate, the expression of these homeodomain proteins covers each individual male-specific neuron. We show that the male-specific nervous system can be subdivided along the anterior/posterior axis in HOX cluster expression domains. The extent of our expression analysis predicts that each individual neuron class is likely defined by unique combinations of homeodomain proteins. Using a collection of newly available molecular markers, we undertake a mutant analysis of five of these genes ( and identified defects in cell fate specification and/or male copulatory defects in each of these mutant strains. Our analysis expands our understanding of the importance of homeobox genes in nervous system development and function.
我们在此探讨在秀丽隐杆线虫庞大但研究较少的雄性特异性神经系统背景下，神经元细胞类型多样性是如何通过基因来界定的。在胚胎后期发育过程中，雄性线虫主要在由294个神经元（116个基本类别）组成的、主要在胚胎期产生的、两性共有的神经系统基础上，添加了93个雄性特异性神经元，这些神经元分为25个基本类别。利用工程改造的报告基因等位基因，我们在此研究了40种系统发育保守的同源结构域蛋白在秀丽隐杆线虫雄性特异性神经系统中的表达模式，结果表明，总体而言，这些同源结构域蛋白的表达覆盖了每一个雄性特异性神经元。我们发现，雄性特异性神经系统可以沿着前后轴在HOX基因簇表达域中进行细分。我们的表达分析结果预测，每个单独的神经元类别可能由同源结构域蛋白的独特组合所定义。利用一系列新获得的分子标记，我们对其中五个基因进行了突变分析，并在每个突变菌株中鉴定出细胞命运特化缺陷和/或雄性交配缺陷。我们的分析扩展了我们对同源框基因在神经系统发育和功能中的重要性的理解。
