The role of Wnt5a in prostate gland development
| Autor: | Terry P. Yamaguchi, Gail S. Prins, Douglas Luccio-Camelo, Liwei Huang, Yongbing Pu, Lynn Birch, Wen-Yang Hu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Cellular differentiation Rats Sprague-Dawley Mice Prostate development 0302 clinical medicine Prostate Prostate gland Cell polarity Testosterone Mice Knockout Extracellular Matrix Proteins 0303 health sciences Estradiol Wnt signaling pathway Cell Polarity Cell Differentiation Cell biology WNT5A medicine.anatomical_structure 030220 oncology & carcinogenesis embryonic structures Intercellular Signaling Peptides and Proteins medicine.medical_specialty Mesenchyme Morphogenesis Biology Cell fate determination Wnt-5a Protein Article 03 medical and health sciences Organ Culture Techniques Internal medicine medicine Animals Hedgehog Proteins RNA Messenger Molecular Biology Adaptor Proteins Signal Transducing 030304 developmental biology Cell Biology Wnt5a Antigens Differentiation Rats Mice Inbred C57BL Wnt Proteins body regions Endocrinology Animals Newborn sense organs Developmental Biology |
| Zdroj: | Developmental Biology. 328(2):188-199 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2009.01.003 |
| Popis: | The Wnt genes encode a large family of secreted glycoproteins that play important roles in controlling tissue patterning, cell fate and proliferation during development. Currently, little is known regarding the role(s) of Wnt genes during prostate gland development. The present study examines the role of the noncanonical Wnt 5a during prostate gland development in rat and murine models. In the rat prostate, Wnt 5a mRNA is expressed by distal mesenchyme during the budding stage and localizes to periductal mesenchymal cells with an increasing proximal-to-distal gradient during branching morphogenesis. Wnt 5a protein is secreted and localizes to periductal stroma, extracellular matrix and epithelial cells in the distal ducts. While Wnt 5a expression is high during active morphogenesis in all prostate lobes, ventral prostate (VP) expression declines rapidly following morphogenesis while dorsal (DP) and lateral lobe (LP) expression remains high into adulthood. Steroids modulate prostatic Wnt 5a expression during early development with testosterone suppressing Wnt 5a and neonatal estrogen increasing expression. In vivo and ex vivo analyses of developing mouse and rat prostates were used to assess the functional roles of Wnt 5a. Wnt 5a −/− murine prostates rescued by organ culture exhibit disturbances in bud position and directed outgrowth leading to large bulbous sacs in place of elongating ducts. In contrast, epithelial cell proliferation, ductal elongation and branchpoint formation are suppressed in newborn rat prostates cultured with exogenous Wnt 5a protein. While renal grafts of Wnt 5a −/− murine prostates revealed that Wnt 5a is not essential for cyto- and functional differentiation, a role in luminal cell polarity and lumenization of the ducts was indicated. Wnt 5a suppresses prostatic Shh expression while Shh stimulates Wnt 5a expression in a lobe-specific manner during early development indicating that Wnt 5a participates in cross-talk with other members of the gene regulatory network that control prostate development. Although Wnt 5a does not influence prostatic expression of other Wnt morphogens, it suppresses Wif -1 expression and can thus indirectly modulate Wnt signaling. In summary, the present finds demonstrate that Wnt 5a is essential for normal prostate development where it regulates bud outgrowth, ductal elongation, branching, cell polarity and lumenization. These findings contribute to the growing body of knowledge on regulatory mechanisms involved in prostate gland development which are key to understanding abnormal growth processes associated with aging. |
| Databáze: | OpenAIRE |
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