Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis

David M. Berman, Nishita Desai, Xi Wang, Sunil S. Karhadkar, Melissa Reynon, Cory Abate-Shen, Philip A. Beachy, Michael M. Shen

Research output: Contribution to journalArticle

Abstract

Previous studies have demonstrated that the Hedgehog (Hh) signaling pathway plays a critical role in the development and patterning of many endodermally derived tissues. We have investigated the role of Sonic hedgehog (Shh) in formation of the prostate gland by examining the urogenital phenotype of Shh mutant fetuses. Consistent with earlier work reporting an essential role for Shh in prostate induction, we have found that Shh mutant fetuses display abnormal urogenital development and fail to form prostate buds. Unexpectedly, however, we have discovered that this prostate defect could be rescued by three different methods: renal grafting, explant culture in the presence of androgens, and administration of dihydrotestosterone (DHT) to pregnant mice, indicating that the prostate defect in Shh mutants is due to insufficient levels of androgens. Furthermore, we find that the inhibition of Hh pathway signaling by treatment with cyclopamine does not block prostate formation in explant culture, but instead produces morphological defects consistent with a role for Hh signaling in ductal patterning. Taken together, our studies indicate that the initial organogenesis of the prostate proceeds independently of Shh, but that Shh or other Hh ligands may play a role in subsequent events that pattern the prostate.

Original languageEnglish (US)
Pages (from-to)387-398
Number of pages12
JournalDevelopmental Biology
Volume267
Issue number2
DOIs
StatePublished - Mar 15 2004

Keywords

  • Androgens
  • Ductal morphogenesis
  • Endoderm
  • Hedgehog
  • Organogenesis
  • Tissue recombination

ASJC Scopus subject areas

  • Developmental Biology

Fingerprint Dive into the research topics of 'Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis'. Together they form a unique fingerprint.

  • Cite this

    Berman, D. M., Desai, N., Wang, X., Karhadkar, S. S., Reynon, M., Abate-Shen, C., Beachy, P. A., & Shen, M. M. (2004). Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis. Developmental Biology, 267(2), 387-398. https://doi.org/10.1016/j.ydbio.2003.11.018