Bettenhausen B, Hrabĕ de Angelis M, Simon D, Guénet J L, Gossler A
Max-Delbrück-Laboratorium in der MPG, Köln, Germany.
Development. 1995 Aug;121(8):2407-18. doi: 10.1242/dev.121.8.2407.
The Drosophila Delta (Dl) gene is essential for cell-cell communication regulating the determination of various cell fates during development. Dl encodes a transmembrane protein, which contains tandem arrays of epidermal-growth-factor-like repeats in the extracellular domain and directly interacts with Notch, another transmembrane protein with similar structural features, in a ligand-receptor-like manner. Similarly, cell-cell interactions involving Delta-like and Notch-like proteins are required for cell fate determinations in C. elegans. Notch homologues were also isolated from several vertebrate species, suggesting that cell-to-cell signaling mediated by Delta- and Notch-like proteins could also underlie cell fate determination during vertebrate development. However, in vertebrates, no Delta homologues have yet been described. We have isolated a novel mouse gene, Dll1 (delta-like gene 1), which maps to the mouse t-complex and whose deduced amino acid sequence strongly suggests that Dll1 represents a mammalian gene closely related to Drosophila Delta. Dll1 is transiently expressed during gastrulation and early organogenesis, and in a tissue-restricted manner in adult animals. Between day 7 and 12.5 of development, expression was detected in the paraxial mesoderm, closely correlated with somitogenesis, and in subsets of cells in the nervous system. In adult animals, transcripts were detected in lung and heart. Dll1 expression in the paraxial mesoderm and nervous system is strikingly similar to the expression of mouse Notch1 during gastrulation and early organogenesis. The overlapping expression patterns of the Dll1 and Notch1 genes suggest that cells in these tissues can communicate by interaction of the Dll1 and Notch1 proteins. Our results support the idea that Delta- and Notch-like proteins are involved in cell-to-cell communication in mammalian embryos and suggest a role for these proteins in cellular interactions underlying somitogenesis and development of the nervous system.
果蝇Delta（Dl）基因对于细胞间通讯至关重要，该通讯在发育过程中调节各种细胞命运的决定。Dl编码一种跨膜蛋白，其胞外结构域包含串联排列的表皮生长因子样重复序列，并以配体-受体样方式直接与Notch（另一种具有相似结构特征的跨膜蛋白）相互作用。同样，秀丽隐杆线虫中细胞命运的决定也需要涉及Delta样和Notch样蛋白的细胞间相互作用。从几种脊椎动物物种中也分离出了Notch同源物，这表明由Delta样和Notch样蛋白介导的细胞间信号传导也可能是脊椎动物发育过程中细胞命运决定的基础。然而，在脊椎动物中，尚未描述Delta同源物。我们分离出了一个新的小鼠基因Dll1（delta样基因1），它定位于小鼠t复合体，其推导的氨基酸序列强烈表明Dll1代表一个与果蝇Delta密切相关的哺乳动物基因。Dll1在原肠胚形成和早期器官发生过程中短暂表达，并在成年动物中以组织限制性方式表达。在发育的第7天至12.5天之间，在近轴中胚层中检测到表达，与体节形成密切相关，并且在神经系统的细胞亚群中也有表达。在成年动物中，在肺和心脏中检测到转录本。Dll1在近轴中胚层和神经系统中的表达与原肠胚形成和早期器官发生过程中小鼠Notch1的表达惊人地相似。Dll1和Notch1基因重叠的表达模式表明这些组织中的细胞可以通过Dll1和Notch1蛋白相互作用进行通讯。我们的结果支持这样的观点，即Delta样和Notch样蛋白参与哺乳动物胚胎中的细胞间通讯，并表明这些蛋白在体节形成和神经系统发育的细胞相互作用中发挥作用。
