Sex specific retinoic acid signaling is required for the initiation of urogenital sinus bud development.
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Date
2014-11-15ICR Author
Author
Bryant, SL
Francis, JC
Lokody, IB
Wang, H
Risbridger, GP
Loveland, KL
Swain, A
Type
Journal Article
Metadata
Show full item recordAbstract
The mammalian urogenital sinus (UGS) develops in a sex specific manner, giving rise to the prostate in the male and the sinus vagina in the embryonic female. Androgens, produced by the embryonic testis, have been shown to be crucial to this process. In this study we show that retinoic acid signaling is required for the initial stages of bud development from the male UGS. Enzymes involved in retinoic acid synthesis are expressed in the UGS mesenchyme in a sex specific manner and addition of ligand to female tissue is able to induce prostate-like bud formation in the absence of androgens, albeit at reduced potency. Functional studies in mouse organ cultures that faithfully reproduce the initiation of prostate development indicate that one of the roles of retinoic acid signaling in the male is to inhibit the expression of Inhba, which encodes the βA subunit of Activin, in the UGS mesenchyme. Through in vivo genetic analysis and culture studies we show that inhibition of Activin signaling in the female UGS leads to a similar phenotype to that of retinoic acid treatment, namely bud formation in the absence of androgens. Our data also reveals that both androgens and retinoic acid have extra independent roles to that of repressing Activin signaling in the development of the prostate during fetal stages. This study identifies a novel role for retinoic acid as a mesenchymal factor that acts together with androgens to determine the position and initiation of bud development in the male UGS epithelia.
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Subject
Urogenital System
Prostate
Animals
Mice
Tretinoin
Activins
Inhibin-beta Subunits
beta-Galactosidase
DNA Primers
Immunohistochemistry
In Situ Hybridization
Sex Factors
Signal Transduction
Organogenesis
Female
Male
Real-Time Polymerase Chain Reaction
Research team
Development & Cancer
Language
eng
Date accepted
2014-09-17
License start date
2014-11
Citation
Developmental biology, 2014, 395 (2), pp. 209 - 217
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE