The Experts below are selected from a list of 873 Experts worldwide ranked by ideXlab platform
Sanjay K. Nigam - One of the best experts on this subject based on the ideXlab platform.
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protein kinase a regulates gdnf ret dependent but not gdnf ret independent ureteric bud outgrowth from the Wolffian Duct
Developmental Biology, 2010Co-Authors: Yohan Choi, Mita M Shah, Ankur V Dnyanmote, Derina E Sweeney, Tom F Gallegos, Kohei Johkura, Kevin T Bush, Sanjay K. NigamAbstract:Abstract Embryonic kidney development begins with the outgrowth of the ureteric bud (UB) from the Wolffian Duct (WD) into the adjacent metanephric mesenchyme (MM). Both a GDNF-dependent and GDNF-independent (Maeshima et al., 2007) pathway have been identified. In vivo and in vitro, the GDNF-dependent pathway is inhibited by BMPs, one of the factors invoked to explain the limitation of UB formation in the unbudded regions of the WD surrounding the UB. However, the exact mechanism remains unknown. Here a previously described in vitro system that models UB budding from the WD was utilized to study this process. Because Protein kinase A (PKA) activation has been shown to prevent migration, morphogenesis and tubulogenesis of epithelial cells (Santos et al., 1993), its activity in budded and non-budded portions of the GDNF-induced WD was analyzed. The level of PKA activity was 15-fold higher in the unbudded portions of the WD compared to budded portions, suggesting that PKA activity plays a key role in controlling the site of UB emergence. Using well-characterized PKA agonists and antagonists, we demonstrated that at various levels of the PKA-signaling hierarchy, PKA regulates UB outgrowth from the WD by suppressing budding events. This process appeared to be PKA-2 isoform specific, and mediated by changes in the Duct rather than the surrounding mesenchyme. In addition, it was not due to changes in either the sorting of junctional proteins, cell death, or cell proliferation. Furthermore, the suppressive effect of cAMP on budding did not appear to be mediated by spread to adjacent cells via gap junctions. Conversely, antagonism of PKA activity stimulated UB outgrowth from the WD and resulted in both an increase in the number of buds per unit length of WD as well as a larger surface area per bud. Using microarrays, analysis of gene expression in GDNF-treated WDs in which the PKA pathway had been activated revealed a nearly 14-fold decrease in Ret, a receptor for GDNF. A smaller decrease in GFRα1. a co-receptor for GDNF, was also observed. Using Ret-null WDs, we were able to demonstrate that PKA regulated GDNF-dependent budding but not GDNF-independent pathway for WD budding. We also found that BMP2 was higher in unbudded regions of the GDNF-stimulated WD. Treatment of isolated WDs with BMP2 suppressed budding and resulted in a 3-fold increase in PKA activity. The data suggests that the suppression of budding by BMPs and possibly other factors in non-budded zones of the WD may be regulated in part by increased PKA activity, probably partially through downregulation of Ret/GFRα1 coreceptor expression.
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glial cell derived neurotrophic factor independent ureteric bud outgrowth from the Wolffian Duct
Journal of The American Society of Nephrology, 2007Co-Authors: Akito Maeshima, Hiroyuki Sakurai, Yohan Choi, Shinji Kitamura, James B. Tee, Duke A Vaughn, Sanjay K. NigamAbstract:The kidney collecting Duct system and the ureter derive from the ureteric bud, an outgrowth of the Wolffian Duct. It is generally believed that glial cell–derived neurotrophic factor (GDNF) plays a critical role in this earliest stage of kidney development, but 30 to 50% of knockout mice that lack
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activin a is an endogenous inhibitor of ureteric bud outgrowth from the Wolffian Duct
Developmental Biology, 2006Co-Authors: Akito Maeshima, Yohan Choi, Duke A Vaughn, Sanjay K. NigamAbstract:Development of metanephric kidney begins with ureteric bud outgrowth from the Wolffian Duct (WD). GDNF is believed to be a crucial positive signal in the budding process, but the negative regulation of this process remains unclear. Here, we examined the role of activin A, a member of TGF-β family, in bud formation using an in vitro WD culture system. When cultured with the surrounding mesonephros, WDs formed many ectopic buds in response to GDNF. While the activin signaling pathway is normally active along the non-budding WD (as measured by expression of activin A and phospho-Smad2/3), activin A was absent and phospho-Smad2/3 was undetectable in the ectopic buds induced by GDNF. To examine the role of activin A in bud formation, we attempted to inactivate activin action. Interestingly, the addition of neutralizing anti-activin A antibody potentiated GDNF action. To further clarify the role of activin A, we also tested the effect of activin blockade on the WD cultured in the absence of mesonephros. WDs without mesonephros did not form ectopic buds even in the presence of GDNF. In contrast, blockade of activin action with a variety of agents acting through different mechanisms (natural antagonist, neutralizing antibodies, siRNA) enabled GDNF to induce ectopic buds. Inhibition of GDNF-induced bud formation by activin A was accompanied by inhibition of cell proliferation, reduced expression of Pax-2, and decreased phosphorylation of PI3-kinase and MAP kinase in the WD. Our data suggest that activin A is an endogenous inhibitor of bud formation and that cancellation of activin A autocrine action may be critical for the initiation of this process.
Frank Costantini - One of the best experts on this subject based on the ideXlab platform.
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Fgf10 expression and function in early ureter and kidney development.
2013Co-Authors: Odyssé Michos, Jonathan D. Licht, Cristina Cebrian, Deborah Hyink, Uta Grieshammer, Linda Williams, Vivette D'agati, Gail R. Martin, Frank CostantiniAbstract:(A,B) In situ hybridization in transverse sections of E10.5 wild type embryos reveals that Fgf10 and Gdnf are expressed in metanephric mesenchyme (arrows). (C,D) Whole-mount in situ hybridization at E11.0 (dorsal view) shows that Fgf10 and Gdnf are expressed in metanephric mesenchyme (MM) surrounding the UB epithelium. The schematic diagram illustrates Fgf10 expression, with purple indicating where the hybridization signal was detected. (E–G) Visualization of Hoxb7/myrVenus shows (E) normal UB branching in an Fgf10+/− kidney, (F) reduced branching in an Fgf10−/− kidney, and (G) rescue of UB branching in an Fgf10−/− kidney when Spry1 dosage is reduced (Spry1+/−). Scale bars, 100 µm. (H–J) InDuction of ectopic budding from the Wolffian Duct by FGF10. Dissected E10.5 urogenital regions were cultured with control PBS-soaked beads (H) or beads soaked in FGF10 (I,J) placed between the two Wolffian Ducts (dotted yellow circles). FGF10 induces multiple ectopic UB outgrowths (marked by asterisks) in both control Gdnf+/− (I) and Gdnf−/− (J) samples. Open arrowhead in H, Wolffian Duct; arrows in H-I, normal ureteric buds.
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Abnormal branching of double mutant kidneys in organ culture.
2013Co-Authors: Odyssé Michos, Jonathan D. Licht, Cristina Cebrian, Deborah Hyink, Uta Grieshammer, Linda Williams, Vivette D'agati, Gail R. Martin, Frank CostantiniAbstract:Kidneys of wild-type (A) and mutant genotypes (B–D), carrying Hoxb7/myrVenus, were excised at E12.5, cultured in vitro, and photographed at the indicated times. The Ret−/− Wolffian Duct (B) failed to develop a ureter or kidney, while the Spry1−/− kidney (C) has multiple ureters (arrowheads), swollen UB tips and an enlarged common nephric Duct (cnd). (D), in two examples of Gdnf−/−;Spry1−/− mutant kidneys, UB branching is retarded at E12.5, and subsequent branching in culture displays abnormal patterns (asterisks and arrowheads – see text) compared to wild-type.
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Genital tract anomalies in Gata3ND−/− embryos.
2013Co-Authors: David Grote, Xuan Chi, Frank Costantini, Sami Kamel Boualia, Abdallah Souabni, Calli Merkel, Thomas Carroll, Maxime BouchardAbstract:(A, B) β-Galactosidase staining of E14.5 genital ridges marks the beginning of Wolffian Duct hyperplasia in male Gata3ND−/− embryos (red arrowhead in B). (C, D) Immunostainings for the mitosis marker phosphorylated Histone H3 (p-H3) show an increase in cell proliferation (n = 4, P = 0.09, Student's t-test) in Gata3ND−/− nephric Ducts at E13.5. E-cadherin labeling marks the genital tracts. (E–H) Whole-mount in situ hybridizations for Emx2 (E, F) or Wnt4 (G, H) of control and Gata3ND−/− E13.5 genital ridges reveal an arrest of Müllerian Duct elongation (red arrowhead in F, H) in Gata3ND−/− embryos. Notably, the elongation arrest occurs at the level of persisting ectopic ureteric buds (black arrows in B). nd, nephric Duct; md, Müllerian Duct; k, kidney; g, gonad.
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FGF8 is essential for formation of the Ductal system in the male reproDuctive tract
Development (Cambridge England), 2011Co-Authors: Jirouta Kitagaki, Xuan Chi, Frank Costantini, Yutaka Ueda, Nirmala Sharma, Cynthia M. Elder, Erika Truffer, Mark Lewandoski, Alan O. PerantoniAbstract:During development of the urogenital tract, fibroblast growth factor 8 (Fgf8) is expressed in mesonephric tubules, but its role in this tissue remains undefined. An evaluation of previously generated T-Cre-mediated Fgf8-deficient mice (T-Cre; Fgf8(flox/Δ2,3) mice), which lack Fgf8 expression in the mesoderm, revealed that the cranial region of the Wolffian Duct degenerated prematurely and the cranial mesonephric tubules were missing. As a result, the epididymis, vas deferens and efferent Ductules were largely absent in mutant mice. Rarb2-Cre was used to eliminate FGF8 from the mesonephric tubules but to allow expression in the adjacent somites. These mutants retained the cranial end of the Wolffian Duct and formed the epididymis and vas deferens, but failed to elaborate the efferent Ductules, indicating that Fgf8 expression by the mesonephric tubules is required specifically for the formation of the Ductules. Ret knockout mice do not form the ureteric bud, a caudal outgrowth of the Wolffian Duct and progenitor for the collecting Duct network in the kidney, but they do develop the cranial end normally. This indicates that Fgf8, but not Ret, expression is essential to the outgrowth of the cranial mesonephric tubules from the Wolffian Duct and to the development of major portions of the sex accessory tissues in the male reproDuctive tract. Mechanistically, FGF8 functions upstream of Lhx1 expression in forming the nephron, and analysis of Fgf8 mutants similarly shows deficient Lhx1 expression in the mesonephric tubules. These results demonstrate a multifocal requirement for FGF8 in establishing the male reproDuctive tract Ducts and implicate Lhx1 signaling in tubule elongation.
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The transcription factors Etv4 and Etv5 mediate formation of the ureteric bud tip domain during kidney development
Development (Cambridge England), 2010Co-Authors: Satu Kuure, Xuan Chi, Frank CostantiniAbstract:Signaling by the Ret receptor tyrosine kinase promotes cell movements in the Wolffian Duct that give rise to the first ureteric bud tip, initiating kidney development. Although the ETS transcription factors Etv4 and Etv5 are known to be required for mouse kidney development and to act downstream of Ret, their specific functions are unclear. Here, we examine their role by analyzing the ability of Etv4 Etv5 compound mutant cells to contribute to chimeric kidneys. Etv4−/−;Etv5+/− cells show a limited distribution in the caudal Wolffian Duct and ureteric bud, similar to Ret−/− cells, revealing a cell-autonomous role for Etv4 and Etv5 in the cell rearrangements promoted by Ret. By contrast, Etv4−/−;Etv5−/− cells display more severe developmental limitations, suggesting a broad role for Etv4 and Etv5 downstream of multiple signals, which are together important for Wolffian Duct and ureteric bud morphogenesis.
Yohan Choi - One of the best experts on this subject based on the ideXlab platform.
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protein kinase a regulates gdnf ret dependent but not gdnf ret independent ureteric bud outgrowth from the Wolffian Duct
Developmental Biology, 2010Co-Authors: Yohan Choi, Mita M Shah, Ankur V Dnyanmote, Derina E Sweeney, Tom F Gallegos, Kohei Johkura, Kevin T Bush, Sanjay K. NigamAbstract:Abstract Embryonic kidney development begins with the outgrowth of the ureteric bud (UB) from the Wolffian Duct (WD) into the adjacent metanephric mesenchyme (MM). Both a GDNF-dependent and GDNF-independent (Maeshima et al., 2007) pathway have been identified. In vivo and in vitro, the GDNF-dependent pathway is inhibited by BMPs, one of the factors invoked to explain the limitation of UB formation in the unbudded regions of the WD surrounding the UB. However, the exact mechanism remains unknown. Here a previously described in vitro system that models UB budding from the WD was utilized to study this process. Because Protein kinase A (PKA) activation has been shown to prevent migration, morphogenesis and tubulogenesis of epithelial cells (Santos et al., 1993), its activity in budded and non-budded portions of the GDNF-induced WD was analyzed. The level of PKA activity was 15-fold higher in the unbudded portions of the WD compared to budded portions, suggesting that PKA activity plays a key role in controlling the site of UB emergence. Using well-characterized PKA agonists and antagonists, we demonstrated that at various levels of the PKA-signaling hierarchy, PKA regulates UB outgrowth from the WD by suppressing budding events. This process appeared to be PKA-2 isoform specific, and mediated by changes in the Duct rather than the surrounding mesenchyme. In addition, it was not due to changes in either the sorting of junctional proteins, cell death, or cell proliferation. Furthermore, the suppressive effect of cAMP on budding did not appear to be mediated by spread to adjacent cells via gap junctions. Conversely, antagonism of PKA activity stimulated UB outgrowth from the WD and resulted in both an increase in the number of buds per unit length of WD as well as a larger surface area per bud. Using microarrays, analysis of gene expression in GDNF-treated WDs in which the PKA pathway had been activated revealed a nearly 14-fold decrease in Ret, a receptor for GDNF. A smaller decrease in GFRα1. a co-receptor for GDNF, was also observed. Using Ret-null WDs, we were able to demonstrate that PKA regulated GDNF-dependent budding but not GDNF-independent pathway for WD budding. We also found that BMP2 was higher in unbudded regions of the GDNF-stimulated WD. Treatment of isolated WDs with BMP2 suppressed budding and resulted in a 3-fold increase in PKA activity. The data suggests that the suppression of budding by BMPs and possibly other factors in non-budded zones of the WD may be regulated in part by increased PKA activity, probably partially through downregulation of Ret/GFRα1 coreceptor expression.
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glial cell derived neurotrophic factor independent ureteric bud outgrowth from the Wolffian Duct
Journal of The American Society of Nephrology, 2007Co-Authors: Akito Maeshima, Hiroyuki Sakurai, Yohan Choi, Shinji Kitamura, James B. Tee, Duke A Vaughn, Sanjay K. NigamAbstract:The kidney collecting Duct system and the ureter derive from the ureteric bud, an outgrowth of the Wolffian Duct. It is generally believed that glial cell–derived neurotrophic factor (GDNF) plays a critical role in this earliest stage of kidney development, but 30 to 50% of knockout mice that lack
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activin a is an endogenous inhibitor of ureteric bud outgrowth from the Wolffian Duct
Developmental Biology, 2006Co-Authors: Akito Maeshima, Yohan Choi, Duke A Vaughn, Sanjay K. NigamAbstract:Development of metanephric kidney begins with ureteric bud outgrowth from the Wolffian Duct (WD). GDNF is believed to be a crucial positive signal in the budding process, but the negative regulation of this process remains unclear. Here, we examined the role of activin A, a member of TGF-β family, in bud formation using an in vitro WD culture system. When cultured with the surrounding mesonephros, WDs formed many ectopic buds in response to GDNF. While the activin signaling pathway is normally active along the non-budding WD (as measured by expression of activin A and phospho-Smad2/3), activin A was absent and phospho-Smad2/3 was undetectable in the ectopic buds induced by GDNF. To examine the role of activin A in bud formation, we attempted to inactivate activin action. Interestingly, the addition of neutralizing anti-activin A antibody potentiated GDNF action. To further clarify the role of activin A, we also tested the effect of activin blockade on the WD cultured in the absence of mesonephros. WDs without mesonephros did not form ectopic buds even in the presence of GDNF. In contrast, blockade of activin action with a variety of agents acting through different mechanisms (natural antagonist, neutralizing antibodies, siRNA) enabled GDNF to induce ectopic buds. Inhibition of GDNF-induced bud formation by activin A was accompanied by inhibition of cell proliferation, reduced expression of Pax-2, and decreased phosphorylation of PI3-kinase and MAP kinase in the WD. Our data suggest that activin A is an endogenous inhibitor of bud formation and that cancellation of activin A autocrine action may be critical for the initiation of this process.
Xuan Chi - One of the best experts on this subject based on the ideXlab platform.
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Genital tract anomalies in Gata3ND−/− embryos.
2013Co-Authors: David Grote, Xuan Chi, Frank Costantini, Sami Kamel Boualia, Abdallah Souabni, Calli Merkel, Thomas Carroll, Maxime BouchardAbstract:(A, B) β-Galactosidase staining of E14.5 genital ridges marks the beginning of Wolffian Duct hyperplasia in male Gata3ND−/− embryos (red arrowhead in B). (C, D) Immunostainings for the mitosis marker phosphorylated Histone H3 (p-H3) show an increase in cell proliferation (n = 4, P = 0.09, Student's t-test) in Gata3ND−/− nephric Ducts at E13.5. E-cadherin labeling marks the genital tracts. (E–H) Whole-mount in situ hybridizations for Emx2 (E, F) or Wnt4 (G, H) of control and Gata3ND−/− E13.5 genital ridges reveal an arrest of Müllerian Duct elongation (red arrowhead in F, H) in Gata3ND−/− embryos. Notably, the elongation arrest occurs at the level of persisting ectopic ureteric buds (black arrows in B). nd, nephric Duct; md, Müllerian Duct; k, kidney; g, gonad.
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FGF8 is essential for formation of the Ductal system in the male reproDuctive tract
Development (Cambridge England), 2011Co-Authors: Jirouta Kitagaki, Xuan Chi, Frank Costantini, Yutaka Ueda, Nirmala Sharma, Cynthia M. Elder, Erika Truffer, Mark Lewandoski, Alan O. PerantoniAbstract:During development of the urogenital tract, fibroblast growth factor 8 (Fgf8) is expressed in mesonephric tubules, but its role in this tissue remains undefined. An evaluation of previously generated T-Cre-mediated Fgf8-deficient mice (T-Cre; Fgf8(flox/Δ2,3) mice), which lack Fgf8 expression in the mesoderm, revealed that the cranial region of the Wolffian Duct degenerated prematurely and the cranial mesonephric tubules were missing. As a result, the epididymis, vas deferens and efferent Ductules were largely absent in mutant mice. Rarb2-Cre was used to eliminate FGF8 from the mesonephric tubules but to allow expression in the adjacent somites. These mutants retained the cranial end of the Wolffian Duct and formed the epididymis and vas deferens, but failed to elaborate the efferent Ductules, indicating that Fgf8 expression by the mesonephric tubules is required specifically for the formation of the Ductules. Ret knockout mice do not form the ureteric bud, a caudal outgrowth of the Wolffian Duct and progenitor for the collecting Duct network in the kidney, but they do develop the cranial end normally. This indicates that Fgf8, but not Ret, expression is essential to the outgrowth of the cranial mesonephric tubules from the Wolffian Duct and to the development of major portions of the sex accessory tissues in the male reproDuctive tract. Mechanistically, FGF8 functions upstream of Lhx1 expression in forming the nephron, and analysis of Fgf8 mutants similarly shows deficient Lhx1 expression in the mesonephric tubules. These results demonstrate a multifocal requirement for FGF8 in establishing the male reproDuctive tract Ducts and implicate Lhx1 signaling in tubule elongation.
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The transcription factors Etv4 and Etv5 mediate formation of the ureteric bud tip domain during kidney development
Development (Cambridge England), 2010Co-Authors: Satu Kuure, Xuan Chi, Frank CostantiniAbstract:Signaling by the Ret receptor tyrosine kinase promotes cell movements in the Wolffian Duct that give rise to the first ureteric bud tip, initiating kidney development. Although the ETS transcription factors Etv4 and Etv5 are known to be required for mouse kidney development and to act downstream of Ret, their specific functions are unclear. Here, we examine their role by analyzing the ability of Etv4 Etv5 compound mutant cells to contribute to chimeric kidneys. Etv4−/−;Etv5+/− cells show a limited distribution in the caudal Wolffian Duct and ureteric bud, similar to Ret−/− cells, revealing a cell-autonomous role for Etv4 and Etv5 in the cell rearrangements promoted by Ret. By contrast, Etv4−/−;Etv5−/− cells display more severe developmental limitations, suggesting a broad role for Etv4 and Etv5 downstream of multiple signals, which are together important for Wolffian Duct and ureteric bud morphogenesis.
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Ret-dependent cell rearrangements in the Wolffian Duct epithelium initiate ureteric bud morphogenesis.
Developmental Cell, 2009Co-Authors: Xuan Chi, Odyssé Michos, Reena Shakya, Paul Riccio, Hideki Enomoto, Jonathan D. Licht, Naoya Asai, Masahide Takahashi, Nobutaka Ohgami, Masashi KatoAbstract:While the genetic control of renal branching morphogenesis has been extensively described, the cellular basis of this process remains obscure. GDNF/RET signaling is required for ureter and kidney development, and cells lacking Ret are excluded from the tips of the branching ureteric bud in chimeric kidneys. Here, we find that this exclusion results from earlier Ret-dependent cell rearrangements in the caudal Wolffian Duct, which generate a specialized epithelial domain that later emerges as the tip of the primary ureteric bud. By juxtaposing cells with elevated or reduced RET activity, we find that Wolffian Duct cells compete, based on RET signaling levels, to contribute to this domain. At the same time, the caudal Wolffian Duct transiently converts from a simple to a pseudostratified epithelium, a process that does not require Ret. Thus, both Ret-dependent cell movements and Ret-independent changes in the Wolffian Duct epithelium contribute to ureteric bud formation.
Mahesh Mansukhani - One of the best experts on this subject based on the ideXlab platform.
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pax8 and pax2 immunostaining facilitates the diagnosis of primary epithelial neoplasms of the male genital tract
The American Journal of Surgical Pathology, 2011Co-Authors: Guoxia Tong, Diane Hamelebena, Stephen M Lagana, Lara Harik, Jennifer M Oliverkrasinski, Cristina Colarossi, Cristina Magigalluzzi, Lorenzo Memeo, Ming Zhou, Mahesh MansukhaniAbstract:PAX8 and PAX2 are cell-lineage-specific transcription factors that are essential for the development of Wolffian and Mullerian Ducts and have recently emerged as specific diagnostic markers for tumors of renal or Mullerian origin. Little is known about their expression in the Wolffian Duct-derived h
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pax8 and pax2 immunostaining facilitates the diagnosis of primary epithelial neoplasms of the male genital tract
The American Journal of Surgical Pathology, 2011Co-Authors: Guoxia Tong, Diane Hamelebena, Stephen M Lagana, Lara Harik, Jennifer M Oliverkrasinski, Cristina Colarossi, Cristina Magigalluzzi, Lorenzo Memeo, Ming Zhou, Mahesh MansukhaniAbstract:PAX8 and PAX2 are cell-lineage-specific transcription factors that are essential for the development of Wolffian and Mullerian Ducts and have recently emerged as specific diagnostic markers for tumors of renal or Mullerian origin. Little is known about their expression in the Wolffian Duct-derived human male genital tract. We report our findings of PAX8 and PAX2 expression in the epithelium of the normal male genital tract and in epithelial tumors derived therefrom using immunohistochemistry (IHC). We found that PAX8 and PAX2 were expressed in the epithelium of the male genital tract from the rete testis to the ejaculatory Duct. Rare glands in the prostatic central zone, a tissue of purported Wolffian Duct origin, were focally positive for PAX2, but no PAX8 was detected in this area, a finding that may warrant further study. We found diffuse expression of PAX8 and PAX2 in 1 case each of serous cystadenoma of the epididymis, carcinoma of the rete testis, Wolffian adnexal tumor of the seminal vesicle, and endometrioid carcinoma of the seminal vesicle. Neither PAX8 nor PAX2 was detected in the seminiferous tubules and interstitium of the normal testis, nor in Leydig cell tumors (n=6), Sertoli cell tumors (n=2), or 48 of 49 germ cell tumors. One pediatric yolk sac tumor showed focal and weak staining for PAX8. Tumors of mesothelial origin, that is, adenomatoid tumors (n=3) and peritoneal malignant mesotheliomas (n=37) in men, were negative for PAX2 and PAX8. Neither PAX2 nor PAX8 was present in other areas of the prostate. Expression of PAX8 and PAX2 in these primary epithelial neoplasms of the male genital tract is due to their histogenetic relationship with Wolffian or Mullerian Ducts. PAX8 and PAX2 IHC may facilitate the diagnosis of these tumors and should be included in the differential diagnostic IHC panel.
