Wnt Signaling Though Beta-Catenin Is Required for Prostate Lineage Specification

Dev Biol. 2012 Nov 15;371(2):246-55. doi: 10.1016/j.ydbio.2012.08.016. Epub 2012 Aug 30.

Abstract

Androgens initiate a complex network of signals within the UGS that trigger prostate lineage commitment and bud formation. Given its contributions to organogenesis in other systems, we investigated a role for canonical Wnt signaling in prostate development. We developed a new method to achieve complete deletion of beta-catenin, the transcriptional coactivator required for canonical Wnt signaling, in early prostate development. Beta-catenin deletion abrogated canonical Wnt signaling and yielded prostate rudiments that exhibited dramatically decreased budding and failed to adopt prostatic identity. This requirement for canonical Wnt signaling was limited to a brief critical period during the initial molecular phase of prostate identity specification. Deletion of beta-catenin in the adult prostate did not significantly affect organ homeostasis. Collectively, these data establish that beta-catenin and Wnt signaling play key roles in prostate lineage specification and bud outgrowth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Prostate / abnormalities
  • Prostate / cytology
  • Prostate / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Wnt Signaling Pathway*
  • beta Catenin / genetics*
  • beta Catenin / metabolism*

Substances

  • Homeodomain Proteins
  • Hoxb13 protein, mouse
  • Nkx3-1 protein, mouse
  • Transcription Factors
  • beta Catenin