Expression of the von Hippel-Lindau disease tumour suppressor gene during human embryogenesis
Expression of the von Hippel-Lindau disease tumour suppressor gene during human embryogenesis
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DOI：
10.1093/hmg/5.5.639
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发表时间：
1996-05-01
影响因子：
3.5
通讯作者：
Maher, ER
中科院分区：
文献类型：
--
作者：
Richards, FM;Schofield, PN;Maher, ER
血管性希佩尔-林道病（VHL）产物被认为通过拮抗延长蛋白增强的转录延长而下调转录。生殖系VHL基因突变易导致视网膜、小脑和脊髓血管母细胞瘤、肾细胞癌和嗜铬细胞瘤的发展。此外，VHL基因的体细胞失活在散发性肾细胞癌和血管母细胞瘤中是常见的。转录延长的调控是基因表达的重要调控机制，VHL基因可能在胚胎发育过程中调节原癌基因和生长抑制基因的表达。因此，我们通过原位杂交研究在受孕后4、6和10周的人胚胎发生过程中VHL mRNA的表达。尽管VHL mRNA在所有三个胚层中表达，但在中枢神经系统、肾脏、睾丸和肺中观察到强表达。VHL mRNA在肾小管内差异表达，表明VHL基因产物可能在肾脏发育中具有特定作用，两种可变剪接的VHL mRNA，特征为包含（亚型I）或排除为了研究外显子2的两种异构体在胚胎发生过程中是否差异表达，从13例胎儿组织中提取VHL mRNA（8-10周），VHL mRNA在胎儿组织中的定量分布反映了原位杂交所见，两种VHL亚型的比例在组织间相似，虽然VHL基因产物调控的基因尚未确定，我们的研究结果与VHL介导的转录延长控制可能在正常人类发育中发挥作用的假设是一致的。
The von Hippel-Lindau (VHL) disease product is thought to down-regulate transcription by antagonizing elongin-enhanced transcriptional elongation, Germline VHL gene mutations predispose to the development of retinal, cerebellar and spinal haemangioblastomas, renal cell carcinoma and phaeochromocytoma, In addition, somatic inactivation of the VHL gene is frequent in sporadic renal cell carcinoma and haemangioblastoma. Regulation of transcript elongation is an important control mechanism for gene expression and the VHL gene might modify the expression of proto-oncogenes and growth suppressor genes during embryogenesis. We therefore investigated the expression of VHL mRNA during human embryogenesis by in situ hybridization studies at 4, 6 and 10 weeks post conception, Although VHL mRNA was expressed in all three germ layers, strong expression was noted in the central nervous system, kidneys, testis and lung, Within the kidney, VHL mRNA was differentially expressed within renal tubules suggesting that the VHL gene product may have a specific role in kidney development, Two alternatively spliced VHL mRNAs characterized by inclusion (isoform I) or exclusion (isoform II) of exon 2 are transcribed in adult tissues, To investigate if the two isoforms are differentially expressed during embryogenesis, VHL mRNA was reverse transcribed from 13 fetal tissues (8-10 weeks gestation), The quantitative distribution of VHL mRNA within fetal tissues reflected that seen by in situ hybridization and the ratio of the two VHL isoforms was similar between tissues, Although the genes regulated by the VHL gene product have not yet been identified, our findings are compatible with the hypothesis that VHL-mediated control of transcriptional elongation may have a role in normal human development.