Human Molecular Genetics, Vol 5, 639-644, Copyright © 1996 by Oxford University Press
FM Richards, PN Schofield, S Fleming and ER Maher
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.
ARTICLES
Expression of the von Hippel-Lindau disease tumour suppressor gene during human embryogenesis
Cambridge University Department of Pathology, UK.
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