Bustelo X R, Rubin S D, Suen K L, Carrasco D, Barbacid M
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Cell Growth Differ. 1993 Apr;4(4):297-308.
We have examined the expression of the vav protooncogene during mouse embryogenesis using RNase protection assays, in situ hybridization, and immunocytochemical analysis. vav gene transcripts were first detected in E11.5 embryos in the blood-forming islands and megakaryocytes of the fetal liver. During diversification of hematopoietic activity in the embryo, vav gene expression became down-regulated in the liver and activated in thymus and spleen. In newborn animals, vav expression was also confined to hematopoietic tissues, with the exception of the ameloblastic cell layer at the latest stages of tooth morphogenesis. In the adult, vav transcripts were found in spleen, thymus, lymph nodes, and bone marrow, but not in liver. In spleen, vav transcripts were concentrated in the white pulp areas, whereas in the red pulp, the vav transcripts appeared to be primarily localized in the megakaryocytes. In thymus, vav expression was found to be more abundant in the cortical areas than in the medulla. In agreement with these observations, purified thymic lymphocytes showed heterogeneous immunoreactivity against the Vav protein, whereas splenic lymphocytes and bone marrow-derived cells displayed rather uniform levels of expression. These observations suggest that the vav protooncogene plays an important role in the signal transduction pathways that regulate the development and maintenance of the hematopoietic system.
我们使用核糖核酸酶保护分析、原位杂交和免疫细胞化学分析方法,检测了小鼠胚胎发育过程中vav原癌基因的表达情况。vav基因转录本首先在E11.5胚胎的胎儿肝脏造血岛和巨核细胞中被检测到。在胚胎造血活动多样化过程中,vav基因表达在肝脏中下调,而在胸腺和脾脏中被激活。在新生动物中,vav表达也局限于造血组织,牙齿形态发生后期的成釉细胞层除外。在成体中,vav转录本存在于脾脏、胸腺、淋巴结和骨髓中,但不存在于肝脏中。在脾脏中,vav转录本集中在白髓区域,而在红髓中,vav转录本似乎主要定位于巨核细胞。在胸腺中,发现vav表达在皮质区域比在髓质中更丰富。与这些观察结果一致,纯化的胸腺淋巴细胞对Vav蛋白显示出异质性免疫反应,而脾淋巴细胞和骨髓来源的细胞则表现出相当一致的表达水平。这些观察结果表明,vav原癌基因在调节造血系统发育和维持的信号转导途径中起重要作用。