Maroulakou I G, Papas T S, Green J E
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702-1201.
Oncogene. 1994 Jun;9(6):1551-65.
ets-1 and ets-2 genes have previously been identified by their sequence homology to the v-ets oncogene of the avian erythroblastosis virus, E26. These cellular genes have been shown to function as transcription factors important in lymphoid differentiation and activation and cellular proliferation. In this study, we have broadly analysed the differential expression of ets-1 and ets-2 during murine development using in situ hybridization. Our results indicate that these transcription factors are expressed in multiple tissues during critical stages of embryo formation and organogenesis, suggesting that these genes may serve multiple functions during mouse development. The patterns of expression of both genes are quite different as early as day 8.0 of gestation. ets-1 expression is clearly observed during a narrow developmental stage in the developing nervous system, including the presumptive hindbrain regions, the neural tube, as well as neural crest and the first and second branchial arches, ets-2 expression is limited to the developing limb buds and distal tail. At later times, ets-1 expression is observed in developing vascular structures, including the heart, arteries, capillaries and meninges, whereas ets-2 is highly expressed in developing bone, tooth buds, epithelial layers of the gut, nasal sinus and uterus, and several regions of the developing brain. Both ets-1 and ets-2 are expressed in developing lung, gut and skin. High levels of expression in both genes is observed in adult lymphoid tissues, but in different tissue subsets. ets-1 is expressed in the adult lung, gut mesenchyme and bone marrow. ets-2 continues to be expressed at low levels in several adult tissues, except in the differentiated brain, where substantial levels of expression are found in particular regions of the mature brain. These results demonstrate that ets-1 and ets-2 are differentially regulated, are widely expressed in many tissues during murine embryogenesis and may play important roles in cellular proliferation and differentiation during mouse development.
ets-1和ets-2基因先前已通过与禽成红细胞增多症病毒E26的v-ets癌基因的序列同源性得以鉴定。这些细胞基因已被证明作为转录因子在淋巴细胞分化、激活及细胞增殖过程中发挥重要作用。在本研究中,我们利用原位杂交技术广泛分析了ets-1和ets-2在小鼠发育过程中的差异表达。我们的结果表明,这些转录因子在胚胎形成和器官发生的关键阶段在多种组织中表达,提示这些基因可能在小鼠发育过程中发挥多种功能。早在妊娠第8.0天时,这两个基因的表达模式就有很大差异。在发育中的神经系统的一个狭窄发育阶段,包括假定的后脑区域、神经管以及神经嵴和第一、第二鳃弓中可清楚观察到ets-1的表达,ets-2的表达则局限于发育中的肢芽和尾尖。在稍后阶段,在发育中的血管结构中可观察到ets-1的表达,包括心脏、动脉、毛细血管和脑膜,而ets-2在发育中的骨骼、牙胚、肠道上皮层、鼻窦和子宫以及发育中脑的几个区域中高表达。ets-1和ets-2在发育中的肺、肠道和皮肤中均有表达。在成年淋巴组织中观察到这两个基因均有高水平表达,但在不同的组织亚群中。ets-1在成年肺、肠道间充质和骨髓中表达。ets-2在几种成年组织中继续低水平表达,除了在分化的脑中,在成熟脑的特定区域可发现其大量表达。这些结果表明,ets-1和ets-2受到差异调节,在小鼠胚胎发育过程中在许多组织中广泛表达,并且可能在小鼠发育过程中的细胞增殖和分化中发挥重要作用。