p63 (TP73L) a key player in embryonic urogential development with significant dysregulation in human bladder exstrophy tissue

  • Authors:
    • Bonnie J. Ching
    • Lars Wittler
    • Judith Proske
    • Garima Yagnik
    • Lihong Qi
    • Markus Draaken
    • Heiko Reutter
    • John P. Gearhart
    • Michael Ludwig
    • Simeon A. Boyadjiev
  • View Affiliations

  • Published online on: December 1, 2010     https://doi.org/10.3892/ijmm_00000535
  • Pages:861-867
0

Abstract

Human bladder exstrophy-epispadias complex (BEEC) comprises a spectrum of urogenital anomalies in which part or all of the distal urinary tract fails to close. Several lines of evidence implicate genetic factors in the formation of BEEC. Among them a murine p63+/+ knockout model showed the full picture of classic exstrophy of the bladder and other urogenital defects within the BEEC spectrum. This led us to study in depth the role of p63 in urogenital development in mice and investigate the implication of p63 in human BEEC. Whole mount in situ analysis in mice was carried out to investigate the ventro-caudal expression of the p63 transcript at gestational days (GD) 9.5-12.5, the equivalent of human gestational weeks 4-6 (postulated time of BEEC organogenesis in humans). In addition, p63 expression analysis was performed in human blood and bladder derived samples of 15 BEEC newborns accompanied by sequencing analysis of their genomic DNA. We also conducted sequencing analysis of genomic DNA in additional 22 BEEC patients. In mouse embryos, p63 expression was detected at days 9.5-12.5 in the cloacal membrane and urethral epithelium, supporting its role in the morphogenesis of the external genitalia and the bladder. Tissue-specific expression of a novel and already-known mRNA isoforms were established and a reproducible dysregulation of variable p63 isoforms was observed in 11 of 15 patients indicating altered gene expression. However, no obvious p63 gene mutations were identified in any of the patients. Our findings strongly suggest that p63 is not only involved in embryonic formation of the urogenital and ventrocaudal anatomy but is also highly dysregulated in human BEEC bladder tissue. Since p63 has been shown to self-regulate its expression through a balance of its isoforms, the dysregulation observed may contribute to the formation of BEEC.

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December 2010
Volume 26 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

2016 Impact Factor: 2.341
Ranked #21/128 Medicine Research and Experimental
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APA
Ching, B.J., Wittler, L., Proske, J., Yagnik, G., Qi, L., Draaken, M. ... Boyadjiev, S.A. (2010). p63 (TP73L) a key player in embryonic urogential development with significant dysregulation in human bladder exstrophy tissue . International Journal of Molecular Medicine, 26, 861-867. https://doi.org/10.3892/ijmm_00000535
MLA
Ching, B. J., Wittler, L., Proske, J., Yagnik, G., Qi, L., Draaken, M., Reutter, H., Gearhart, J. P., Ludwig, M., Boyadjiev, S. A."p63 (TP73L) a key player in embryonic urogential development with significant dysregulation in human bladder exstrophy tissue ". International Journal of Molecular Medicine 26.6 (2010): 861-867.
Chicago
Ching, B. J., Wittler, L., Proske, J., Yagnik, G., Qi, L., Draaken, M., Reutter, H., Gearhart, J. P., Ludwig, M., Boyadjiev, S. A."p63 (TP73L) a key player in embryonic urogential development with significant dysregulation in human bladder exstrophy tissue ". International Journal of Molecular Medicine 26, no. 6 (2010): 861-867. https://doi.org/10.3892/ijmm_00000535