Talk:Prostate Development: Difference between revisions

Revision as of 10:57, 28 October 2010

2009

The role of Wnt5a in prostate gland development

Dev Biol. 2009 Apr 15;328(2):188-99. Epub 2009 Jan 14.

Huang L, Pu Y, Hu WY, Birch L, Luccio-Camelo D, Yamaguchi T, Prins GS.

Department of Urology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60614, USA.

Abstract

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 Wnt5a during prostate gland development in rat and murine models. In the rat prostate, Wnt5a 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. Wnt5a protein is secreted and localizes to periductal stroma, extracellular matrix and epithelial cells in the distal ducts. While Wnt5a 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 Wnt5a expression during early development with testosterone suppressing Wnt5a 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 Wnt5a. Wnt5a(-/-) 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 Wnt5a protein. While renal grafts of Wnt5a(-/-) murine prostates revealed that Wnt5a is not essential for cyto- and functional differentiation, a role in luminal cell polarity and lumenization of the ducts was indicated. Wnt5a suppresses prostatic Shh expression while Shh stimulates Wnt5a expression in a lobe-specific manner during early development indicating that Wnt5a participates in cross-talk with other members of the gene regulatory network that control prostate development. Although Wnt5a 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 Wnt5a 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.

PMID: 19389372 PMCID: PMC2828764

http://www.ncbi.nlm.nih.gov/pubmed/19389372

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-==Prostate Histology==
+==2009==
-The prostate is the largest accessory sex gland in men (about 2 × 3 × 4 cm). It contains 30 - 50 tubuloalveolar glands, which empty into 15 - 25 independent excretory ducts. These ducts open into the urethra. The glands are embedded into a fibromuscular stroma, which mainly consists of smooth muscle separated by strands of connective tissue rich in collagenous and elastic fibres. The muscle forms a dense mass around the urethra and beneath the fairly thin capsule of the prostrate.
-The secretory alveoli of the prostate are very irregularly shaped because of papillary projections of the mucosa into the lumen of the gland. The epithelium is cuboidal or columnar. Basal cells are again present, and the epithelium may look pseudostratified where they are found. The secretory cells are slightly acidophilic and secretory granules may be visible in the cytoplasm. Small extensions of the apical cytoplasm into the lumen of the alveoli may represent cells which  release their secretory products (secretion is apocrine/merocine). The secretion of the prostate contains citric acid, the enzyme fibrinolysin (liquefies the semen), acid phosphatase, a number of other enzymes and lipids. The secretion of the prostate is the first fraction of the ejaculate.
+===The role of Wnt5a in prostate gland development===
+Dev Biol. 2009 Apr 15;328(2):188-99. Epub 2009 Jan 14.
-The secretory ducts of the prostate are lined by a simple columnar epithelium, which changes to a transitional epithelium near the openings of the ducts into the urethra.
+Huang L, Pu Y, Hu WY, Birch L, Luccio-Camelo D, Yamaguchi T, Prins GS.
-A characteristic feature of the prostate is the appearance of corpora amylacea in the secretory alveoli. They are rounded eosinophilic bodies. Their average diameter is about 0.25 mm (up to 2 mm). They appear already in the seventh month of foetal development. Their number increases with age - in particular past 50. They may undergo calcification. Corpora amylacea may appear in semen.
+Department of Urology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60614, USA.
-Macroscopically the prostrate can be divided into lobes, but they are inconspicuous in histological sections. In good histological sections it is possible to distinguish three concentric zones, which surround the prostatic part of the urethra.
+Abstract
-The peripheral zone contains large, so-called main glands, whose ducts run posteriorly to open into the urethra.
+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 Wnt5a during prostate gland development in rat and murine models. In the rat prostate, Wnt5a 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. Wnt5a protein is secreted and localizes to periductal stroma, extracellular matrix and epithelial cells in the distal ducts. While Wnt5a 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 Wnt5a expression during early development with testosterone suppressing Wnt5a 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 Wnt5a. Wnt5a(-/-) 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 Wnt5a protein. While renal grafts of Wnt5a(-/-) murine prostates revealed that Wnt5a is not essential for cyto- and functional differentiation, a role in luminal cell polarity and lumenization of the ducts was indicated. Wnt5a suppresses prostatic Shh expression while Shh stimulates Wnt5a expression in a lobe-specific manner during early development indicating that Wnt5a participates in cross-talk with other members of the gene regulatory network that control prostate development. Although Wnt5a 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 Wnt5a 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.
-The internal zone consists of the so-called submucosal glands, whereas
-the innermost zone contains mucosal glands.
-This subdivision of the prostate is of clinical importance. With age the prostate becomes enlarged due to benign nodular hyperplasia. The onset age of these hyperplastic changes is 45. About 3/4 of the males above 60 are affected of which half will be symptomatic. This condition affects the mucosal glands. Cancer of the prostate, which is the second most common malignant tumor in western males, involves the peripheral zone.
-From: [http://www.lab.anhb.uwa.edu.au/mb140/CorePages/MaleRepro/malerepro.htm#Prostate Blue Histology - Prostate]
+PMID: 19389372 PMCID: PMC2828764
+http://www.ncbi.nlm.nih.gov/pubmed/19389372