Krüppel-like factor 6 (Klf6) belongs to a family of zinc finger transcription factors known to play a role in development and tumor suppression. Although Klf6 is highly mutated in prostate cancer, its function in prostate development is unknown. We have generated a prostate-specific Klf6-deficient mouse model and report here a novel role for Klf6 in the regulation of prostate branching morphogenesis. Importantly, our study reveals a novel relationship between Klf6 and the Shh pathway. Klf6-deficiency leads to elevated levels of hedgehog pathway components (Shh, Ptc, and Gli) and loss of their localized expression, which in turn causes impaired lateral branching. Krüppel-like factor 6 (Klf6) belongs to a family of zinc finger transcription factors known to play a role in development and tumor suppression. Although Klf6 is highly mutated in prostate cancer, its function in prostate development is unknown. We have generated a prostate-specific Klf6-deficient mouse model and report here a novel role for Klf6 in the regulation of prostate branching morphogenesis. Importantly, our study reveals a novel relationship between Klf6 and the Shh pathway. Klf6-deficiency leads to elevated levels of hedgehog pathway components (Shh, Ptc, and Gli) and loss of their localized expression, which in turn causes impaired lateral branching. Klf6 belongs to the family of Krüppel-like zinc finger transcription factors that regulate cell proliferation and differentiation (1Bieker J.J. J. Biol. Chem. 2001; 276: 34355-34358Abstract Full Text Full Text PDF PubMed Scopus (531) Google Scholar). All members of the Klf gene family contain a highly conserved zinc finger DNA binding domain at their C terminus and an activation domain at its N terminus, distinct to each Klf gene and accounting for their wide-ranging biological capabilities (2Huber T.L. Perkins A.C. Deconinck A.E. Chan F.Y. Mead P.E. Zon L.I. Curr. Biol. 2001; 11: 1456-1461Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 3Laub F. Aldabe R. Friedrich Jr., V. Ohnishi S. Yoshida T. Ramirez F. Dev. Biol. 2001; 233: 305-318Crossref PubMed Scopus (78) Google Scholar, 4Oates A.C. Pratt S.J. Vail B. Yan Y.I. Ho R.K. Johnson S.L. Postlethwait J.H. Zon L.I. Blood. 2001; 98: 1792-1801Crossref PubMed Scopus (92) Google Scholar). Similar to other members of the Klf family (5Zhao W. Hisamuddin I.M. Nandan M.O. Babbin B.A. Lamb N.E. Yang V.W. Oncogene. 2004; 23: 395-402Crossref PubMed Scopus (263) Google Scholar, 6Chen C. Bhalala H.V. Qiao H. Dong J.T. Oncogene. 2002; 21: 6567-6572Crossref PubMed Scopus (127) Google Scholar), Klf6 is reported to act as a tumor suppressor (7Narla G. Heath K.E. Reeves H.L. Li D. Giono L.E. Kimmelman A.C. Glucksman M.J. Narla J. Eng F.J. Chan A.M. Ferrari A.C. Martignetti J.A. Friedman S.L. Science. 2001; 294: 2563-2566Crossref PubMed Scopus (377) Google Scholar, 8Reeves H.L. Narla G. Ogunbiyi O. Haq A.I. Katz A. Benzeno S. Hod E. Harpaz N. Goldberg S. Tal-Kremer S. Eng F.J. Arthur M.J. Martignetti J.A. Friedman S.L. Gastroenterology. 2004; 126: 1090-1103Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar, 9Kimmelman A.C. Qiao R.F. Narla G. Banno A. Lau N. Bos P.D. Nuñez Rodriguez N. Liang B.C. Guha A. Martignetti J.A. Friedman S.L. Chan A.M. Oncogene. 2004; 23: 5077-5083Crossref PubMed Scopus (67) Google Scholar, 10Ito G. Uchiyama M. Kondo M. Mori S. Usami N. Maeda O. Kawabe T. Hasegawa Y. Shimokata K. Sekido Y. Cancer Res. 2004; 64: 3838-3843Crossref PubMed Scopus (131) Google Scholar). Klf6 has been reported to be mutated in a large percentage of human prostate tumors (7Narla G. Heath K.E. Reeves H.L. Li D. Giono L.E. Kimmelman A.C. Glucksman M.J. Narla J. Eng F.J. Chan A.M. Ferrari A.C. Martignetti J.A. Friedman S.L. Science. 2001; 294: 2563-2566Crossref PubMed Scopus (377) Google Scholar), but its function during normal development has not been elucidated.Prostate development, specifically epithelial branching morphogenesis, is a well studied process. Outgrowth and branching of the prostate epithelial buds into the enveloping mesenchyme occur during the first 3 weeks postnatally (11Sugimura Y. Cunha G.R. Donjacour A.A. Biol. Reprod. 1986; 34: 961-971Crossref PubMed Scopus (311) Google Scholar). The fully developed prostate in an adult mouse is composed of three different paired lobes, referred as the anterior, ventral, and dorsal-lateral lobes. In addition, the number of main ducts and complexity of ductal branching vary among the three lobes. A number of growth factors/pathways have been implicated in regulating prostatic epithelial proliferation and differentiation, including hedgehog (Hh), 4The abbreviations used are: HhhedgehogBMPbone morphogenic proteinFGFfibroblastic growth factorShhsonic hedgehogMicro-CTmicro-computed tomographySMAsmooth muscle actinH&Ehematoxylin and eosinTCRDT-cell receptor delta chain. 4The abbreviations used are: HhhedgehogBMPbone morphogenic proteinFGFfibroblastic growth factorShhsonic hedgehogMicro-CTmicro-computed tomographySMAsmooth muscle actinH&Ehematoxylin and eosinTCRDT-cell receptor delta chain. bone morphogenic proteins (BMPs), fibroblastic growth factors (FGFs), and Notch and Wnt pathways (12Freestone S.H. Marker P. Grace O.C. Tomlinson D.C. Cunha G.R. Harnden P. Thomson A.A. Dev. Biol. 2003; 264: 352-362Crossref PubMed Scopus (128) Google Scholar, 13Wang B.E. Shou J. Ross S. Koeppen H. De Sauvage F.J. Gao W.Q. J. Biol. Chem. 2003; 278: 18506-18513Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 14Berman D.M. Desai N. Wang X. Karhadkar S.S. Reynon M. Abate-Shen C. Beachy P.A. Shen M.M. Dev. Biol. 2004; 267: 387-398Crossref PubMed Scopus (111) Google Scholar, 15Lamm M.L. Catbagan W.S. Laciak R.J. Barnett D.H. Hebner C.M. Gaffield W. Walterhouse D. Iannaccone P. Bushman W. Dev. Biol. 2002; 249: 349-366Crossref PubMed Scopus (137) Google Scholar, 16Thomson A.A. Cunha G.R. Development. 1999; 126: 3693-3701PubMed Google Scholar, 17Lamm M.L. Podlasek C.A. Barnett D.H. Lee J. Clemens J.Q. Hebner C.M. Bushman W. Dev. Biol. 2001; 232: 301-314Crossref PubMed Scopus (124) Google Scholar, 18Wang X.D. Leow C.C. Zha J. Tang Z. Modrusan Z. Radtke F. Aguet M. de Sauvage F.J. Gao W.Q. Dev. Biol. 2006; 290: 66-80Crossref PubMed Scopus (122) Google Scholar, 19Wang B.E. Wang X.D. Ernst J.A. Polakis P. Gao W.Q. PLoS ONE. 2008; 3: e2186Crossref PubMed Scopus (50) Google Scholar). For example, work done in our laboratory and others showed that sonic hedgehog (Shh) produced in the prostatic epithelium is a negative regulator of prostatic branching morphogenesis, mediated indirectly by periepithelial mesenchymal cells (12Freestone S.H. Marker P. Grace O.C. Tomlinson D.C. Cunha G.R. Harnden P. Thomson A.A. Dev. Biol. 2003; 264: 352-362Crossref PubMed Scopus (128) Google Scholar, 13Wang B.E. Shou J. Ross S. Koeppen H. De Sauvage F.J. Gao W.Q. J. Biol. Chem. 2003; 278: 18506-18513Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 14Berman D.M. Desai N. Wang X. Karhadkar S.S. Reynon M. Abate-Shen C. Beachy P.A. Shen M.M. Dev. Biol. 2004; 267: 387-398Crossref PubMed Scopus (111) Google Scholar, 15Lamm M.L. Catbagan W.S. Laciak R.J. Barnett D.H. Hebner C.M. Gaffield W. Walterhouse D. Iannaccone P. Bushman W. Dev. Biol. 2002; 249: 349-366Crossref PubMed Scopus (137) Google Scholar). In addition, while mesenchymal FGF10 stimulates prostatic epithelial growth (16Thomson A.A. Cunha G.R. Development. 1999; 126: 3693-3701PubMed Google Scholar), BMP4 is a mesenchymal factor that inhibits prostatic ductal budding and branching morphogenesis (17Lamm M.L. Podlasek C.A. Barnett D.H. Lee J. Clemens J.Q. Hebner C.M. Bushman W. Dev. Biol. 2001; 232: 301-314Crossref PubMed Scopus (124) Google Scholar).All Klf generated M.L. M.M. C. Dev. 11: PubMed Scopus Google Scholar, B. D. A. R. F. PubMed Scopus Google Scholar, J.A. C. E. 1999; PubMed Scopus Google Scholar), including the Klf6 N. A. H. K. F. Ramirez F. G. Friedman S.L. Blood. 2006; PubMed Scopus Google Scholar). prostate development in and to study the role of Klf6 in prostate development and by a prostate-specific of the Klf6 gene a We report here a novel role for Klf6 in the regulation of epithelial branching morphogenesis in the Klf gene family is known to be for development in A.C. Pratt S.J. Vail B. Yan Y.I. Ho R.K. Johnson S.L. Postlethwait J.H. Zon L.I. Blood. 2001; 98: 1792-1801Crossref PubMed Scopus (92) Google Scholar). in a large number of J. M. 1999; Full Text Full Text PDF PubMed Scopus Google and play an role in the of cell differentiation A.C. Pratt S.J. Vail B. Yan Y.I. Ho R.K. Johnson S.L. Postlethwait J.H. Zon L.I. Blood. 2001; 98: 1792-1801Crossref PubMed Scopus (92) Google Scholar), cell B. D. A. R. F. PubMed Scopus Google Scholar, A.C. S.H. PubMed Scopus (127) Google Scholar), activation M.L. Science. PubMed Scopus Google Scholar), M.L. M.M. C. Dev. 11: PubMed Scopus Google Scholar), and J.A. C. E. 1999; PubMed Scopus Google Scholar). the prostate as a here for the first a role for Klf6 in prostate branching morphogenesis. Klf family has been to be for in the of leads to and of which in and in V. S. T. P. P. J. C. Dev. 2008; PubMed Scopus Google Scholar). In the Klf6 is known to be in the and J.A. J. 2001; PubMed Google Scholar), an that be a role in branching loss of Klf6 is N. A. H. K. F. Ramirez F. G. Friedman S.L. Blood. 2006; PubMed Scopus Google Scholar), generated for Klf6 specifically in the The lateral branching in Klf6-deficient prostate by and a novel to that Klf6 a role in the epithelial and which in of The branching in the known as a which the of Klf6 the in epithelial and not prostatic function has been impaired in to be branching in the prostate is the branching in the prostate distinct the prostate and In addition, the of the prostate is different the other prostate G.R. B. of Scholar, G.R. T. Donjacour A.A. B.A. J. Google Scholar). Although branching of the prostate and to the epithelium into the prostate is to be epithelium at the of the into the mesenchyme of the which is the the in the prostate has distinct the other prostate and as a of lateral and not as a of at the our and others the role of Shh in prostate branching (12Freestone S.H. Marker P. Grace O.C. Tomlinson D.C. Cunha G.R. Harnden P. Thomson A.A. Dev. Biol. 2003; 264: 352-362Crossref PubMed Scopus (128) Google Scholar, 13Wang B.E. Shou J. Ross S. Koeppen H. De Sauvage F.J. Gao W.Q. J. Biol. Chem. 2003; 278: 18506-18513Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 14Berman D.M. Desai N. Wang X. Karhadkar S.S. Reynon M. Abate-Shen C. Beachy P.A. Shen M.M. Dev. Biol. 2004; 267: 387-398Crossref PubMed Scopus (111) Google Scholar, 15Lamm M.L. Catbagan W.S. Laciak R.J. Barnett D.H. Hebner C.M. Gaffield W. Walterhouse D. Iannaccone P. Bushman W. Dev. Biol. 2002; 249: 349-366Crossref PubMed Scopus (137) Google Scholar, Y. Dev. Biol. 2004; PubMed Scopus Google Scholar), to and in in the study that impaired lateral branching in the Klf6-deficient prostate an and loss of of Ptc, and for the of in prostate epithelial branching a study by Bushman and M.L. Catbagan W.S. Laciak R.J. Barnett D.H. Hebner C.M. Gaffield W. Walterhouse D. Iannaccone P. Bushman W. Dev. Biol. 2002; 249: 349-366Crossref PubMed Scopus (137) Google Scholar), a between prostate ductal and localized of Shh at the of prostate In addition, Shh prostate branching morphogenesis in FGF10 and BMP4 Y. Dev. Biol. 2004; PubMed Scopus Google Scholar). Shh the epithelial ductal FGF10 that stimulates epithelial cell growth (16Thomson A.A. Cunha G.R. Development. 1999; 126: 3693-3701PubMed Google BMP4 that inhibits epithelial cell growth (17Lamm M.L. Podlasek C.A. Barnett D.H. Lee J. Clemens J.Q. Hebner C.M. Bushman W. Dev. Biol. 2001; 232: 301-314Crossref PubMed Scopus (124) Google in the which in epithelial ductal branching Y. Dev. Biol. 2004; PubMed Scopus Google Scholar). In the that loss of Klf6 leads to Shh the epithelial ducts and and in the mesenchyme domain of pathway leads to an of BMP4 expression, in ductal branching. by and the and localized of Shh and BMP4 to branching Y. Dev. Biol. 2004; PubMed Scopus Google is reported to be a tumor suppressor that is in a large of prostate G. Friedman S.L. Martignetti J.A. J. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). our of as as to prostate C. B. J. S. M. J. R. A. D. G. M. M. F. J. de and The of tumor in the Klf6 be to other Klf family is that loss of Klf6 not be to prostate in the mouse and that of tumor be Klf6 belongs to the family of Krüppel-like zinc finger transcription factors that regulate cell proliferation and differentiation (1Bieker J.J. J. Biol. Chem. 2001; 276: 34355-34358Abstract Full Text Full Text PDF PubMed Scopus (531) Google Scholar). All members of the Klf gene family contain a highly conserved zinc finger DNA binding domain at their C terminus and an activation domain at its N terminus, distinct to each Klf gene and accounting for their wide-ranging biological capabilities (2Huber T.L. Perkins A.C. Deconinck A.E. Chan F.Y. Mead P.E. Zon L.I. Curr. Biol. 2001; 11: 1456-1461Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 3Laub F. Aldabe R. Friedrich Jr., V. Ohnishi S. Yoshida T. Ramirez F. Dev. Biol. 2001; 233: 305-318Crossref PubMed Scopus (78) Google Scholar, 4Oates A.C. Pratt S.J. Vail B. Yan Y.I. Ho R.K. Johnson S.L. Postlethwait J.H. Zon L.I. Blood. 2001; 98: 1792-1801Crossref PubMed Scopus (92) Google Scholar). Similar to other members of the Klf family (5Zhao W. Hisamuddin I.M. Nandan M.O. Babbin B.A. Lamb N.E. Yang V.W. Oncogene. 2004; 23: 395-402Crossref PubMed Scopus (263) Google Scholar, 6Chen C. Bhalala H.V. Qiao H. Dong J.T. Oncogene. 2002; 21: 6567-6572Crossref PubMed Scopus (127) Google Scholar), Klf6 is reported to act as a tumor suppressor (7Narla G. Heath K.E. Reeves H.L. Li D. Giono L.E. Kimmelman A.C. Glucksman M.J. Narla J. Eng F.J. Chan A.M. Ferrari A.C. Martignetti J.A. Friedman S.L. Science. 2001; 294: 2563-2566Crossref PubMed Scopus (377) Google Scholar, 8Reeves H.L. Narla G. Ogunbiyi O. Haq A.I. Katz A. Benzeno S. Hod E. Harpaz N. Goldberg S. Tal-Kremer S. Eng F.J. Arthur M.J. Martignetti J.A. Friedman S.L. Gastroenterology. 2004; 126: 1090-1103Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar, 9Kimmelman A.C. Qiao R.F. Narla G. Banno A. Lau N. Bos P.D. Nuñez Rodriguez N. Liang B.C. Guha A. Martignetti J.A. Friedman S.L. Chan A.M. Oncogene. 2004; 23: 5077-5083Crossref PubMed Scopus (67) Google Scholar, 10Ito G. Uchiyama M. Kondo M. Mori S. Usami N. Maeda O. Kawabe T. Hasegawa Y. Shimokata K. Sekido Y. Cancer Res. 2004; 64: 3838-3843Crossref PubMed Scopus (131) Google Scholar). Klf6 has been reported to be mutated in a large percentage of human prostate tumors (7Narla G. Heath K.E. Reeves H.L. Li D. Giono L.E. Kimmelman A.C. Glucksman M.J. Narla J. Eng F.J. Chan A.M. Ferrari A.C. Martignetti J.A. Friedman S.L. Science. 2001; 294: 2563-2566Crossref PubMed Scopus (377) Google Scholar), but its function during normal development has not been development, specifically epithelial branching morphogenesis, is a well studied process. Outgrowth and branching of the prostate epithelial buds into the enveloping mesenchyme occur during the first 3 weeks postnatally (11Sugimura Y. Cunha G.R. Donjacour A.A. Biol. Reprod. 1986; 34: 961-971Crossref PubMed Scopus (311) Google Scholar). The fully developed prostate in an adult mouse is composed of three different paired lobes, referred as the anterior, ventral, and dorsal-lateral lobes. In addition, the number of main ducts and complexity of ductal branching vary among the three lobes. A number of growth factors/pathways have been implicated in regulating prostatic epithelial proliferation and differentiation, including hedgehog (Hh), 4The abbreviations used are: HhhedgehogBMPbone morphogenic proteinFGFfibroblastic growth factorShhsonic hedgehogMicro-CTmicro-computed tomographySMAsmooth muscle actinH&Ehematoxylin and eosinTCRDT-cell receptor delta chain. 4The abbreviations used are: HhhedgehogBMPbone morphogenic proteinFGFfibroblastic growth factorShhsonic hedgehogMicro-CTmicro-computed tomographySMAsmooth muscle actinH&Ehematoxylin and eosinTCRDT-cell receptor delta chain. bone morphogenic proteins (BMPs), fibroblastic growth factors (FGFs), and Notch and Wnt pathways (12Freestone S.H. Marker P. Grace O.C. Tomlinson D.C. Cunha G.R. Harnden P. Thomson A.A. Dev. Biol. 2003; 264: 352-362Crossref PubMed Scopus (128) Google Scholar, 13Wang B.E. Shou J. Ross S. Koeppen H. De Sauvage F.J. Gao W.Q. J. Biol. Chem. 2003; 278: 18506-18513Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 14Berman D.M. Desai N. Wang X. Karhadkar S.S. Reynon M. Abate-Shen C. Beachy P.A. Shen M.M. Dev. Biol. 2004; 267: 387-398Crossref PubMed Scopus (111) Google Scholar, 15Lamm M.L. Catbagan W.S. Laciak R.J. Barnett D.H. Hebner C.M. Gaffield W. Walterhouse D. Iannaccone P. Bushman W. Dev. Biol. 2002; 249: 349-366Crossref PubMed Scopus (137) Google Scholar, 16Thomson A.A. Cunha G.R. Development. 1999; 126: 3693-3701PubMed Google Scholar, 17Lamm M.L. Podlasek C.A. Barnett D.H. Lee J. Clemens J.Q. Hebner C.M. Bushman W. Dev. Biol. 2001; 232: 301-314Crossref PubMed Scopus (124) Google Scholar, 18Wang X.D. Leow C.C. Zha J. Tang Z. Modrusan Z. Radtke F. Aguet M. de Sauvage F.J. Gao W.Q. Dev. Biol. 2006; 290: 66-80Crossref PubMed Scopus (122) Google Scholar, 19Wang B.E. Wang X.D. Ernst J.A. Polakis P. Gao W.Q. PLoS ONE. 2008; 3: e2186Crossref PubMed Scopus (50) Google Scholar). For example, work done in our laboratory and others showed that sonic hedgehog (Shh) produced in the prostatic epithelium is a negative regulator of prostatic branching morphogenesis, mediated indirectly by periepithelial mesenchymal cells (12Freestone S.H. Marker P. Grace O.C. Tomlinson D.C. Cunha G.R. Harnden P. Thomson A.A. Dev. Biol. 2003; 264: 352-362Crossref PubMed Scopus (128) Google Scholar, 13Wang B.E. Shou J. Ross S. Koeppen H. De Sauvage F.J. Gao W.Q. J. Biol. Chem. 2003; 278: 18506-18513Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 14Berman D.M. Desai N. Wang X. Karhadkar S.S. Reynon M. Abate-Shen C. Beachy P.A. Shen M.M. Dev. Biol. 2004; 267: 387-398Crossref PubMed Scopus (111) Google Scholar, 15Lamm M.L. Catbagan W.S. Laciak R.J. Barnett D.H. Hebner C.M. Gaffield W. Walterhouse D. Iannaccone P. Bushman W. Dev. Biol. 2002; 249: 349-366Crossref PubMed Scopus (137) Google Scholar). In addition, while mesenchymal FGF10 stimulates prostatic epithelial growth (16Thomson A.A. Cunha G.R. Development. 1999; 126: 3693-3701PubMed Google Scholar), BMP4 is a mesenchymal factor that inhibits prostatic ductal budding and branching morphogenesis (17Lamm M.L. Podlasek C.A. Barnett D.H. Lee J. Clemens J.Q. Hebner C.M. Bushman W. Dev. Biol. 2001; 232: 301-314Crossref PubMed Scopus (124) Google Scholar). hedgehog bone morphogenic fibroblastic growth factor sonic hedgehog muscle and receptor delta chain. hedgehog bone morphogenic fibroblastic growth factor sonic hedgehog muscle and receptor delta chain. All Klf generated M.L. M.M. C. Dev. 11: PubMed Scopus Google Scholar, B. D. A. R. F. PubMed Scopus Google Scholar, J.A. C. E. 1999; PubMed Scopus Google Scholar), including the Klf6 N. A. H. K. F. Ramirez F. G. Friedman S.L. Blood. 2006; PubMed Scopus Google Scholar). prostate development in and to study the role of Klf6 in prostate development and by a prostate-specific of the Klf6 gene a We report here a novel role for Klf6 in the regulation of epithelial branching morphogenesis in the Klf gene family is known to be for development in A.C. Pratt S.J. Vail B. Yan Y.I. Ho R.K. Johnson S.L. Postlethwait J.H. Zon L.I. Blood. 2001; 98: 1792-1801Crossref PubMed Scopus (92) Google Scholar). in a large number of J. M. 1999; Full Text Full Text PDF PubMed Scopus Google and play an role in the of cell differentiation A.C. Pratt S.J. Vail B. Yan Y.I. Ho R.K. Johnson S.L. Postlethwait J.H. Zon L.I. Blood. 2001; 98: 1792-1801Crossref PubMed Scopus (92) Google Scholar), cell B. D. A. R. F. PubMed Scopus Google Scholar, A.C. S.H. PubMed Scopus (127) Google Scholar), activation M.L. Science. PubMed Scopus Google Scholar), M.L. M.M. C. Dev. 11: PubMed Scopus Google Scholar), and J.A. C. E. 1999; PubMed Scopus Google Scholar). the prostate as a here for the first a role for Klf6 in prostate branching morphogenesis. Klf family has been to be for in the of leads to and of which in and in V. S. T. P. P. J. C. Dev. 2008; PubMed Scopus Google Scholar). In the Klf6 is known to be in the and J.A. J. 2001; PubMed Google Scholar), an that be a role in branching loss of Klf6 is N. A. H. K. F. Ramirez F. G. Friedman S.L. Blood. 2006; PubMed Scopus Google Scholar), generated for Klf6 specifically in the The lateral branching in Klf6-deficient prostate by and a novel to that Klf6 a role in the epithelial and which in of The branching in the known as a which the of Klf6 the in epithelial and not prostatic function has been impaired in to be branching in the prostate is the branching in the prostate distinct the prostate and In addition, the of the prostate is different the other prostate G.R. B. of Scholar, G.R. T. Donjacour A.A. B.A. J. Google Scholar). Although branching of the prostate and to the epithelium into the prostate is to be epithelium at the of the into the mesenchyme of the which is the the in the prostate has distinct the other prostate and as a of lateral and not as a of at the our and others the role of Shh in prostate branching (12Freestone S.H. Marker P. Grace O.C. Tomlinson D.C. Cunha G.R. Harnden P. Thomson A.A. Dev. Biol. 2003; 264: 352-362Crossref PubMed Scopus (128) Google Scholar, 13Wang B.E. Shou J. Ross S. Koeppen H. De Sauvage F.J. Gao W.Q. J. Biol. Chem. 2003; 278: 18506-18513Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 14Berman D.M. Desai N. Wang X. Karhadkar S.S. Reynon M. Abate-Shen C. Beachy P.A. Shen M.M. Dev. Biol. 2004; 267: 387-398Crossref PubMed Scopus (111) Google Scholar, 15Lamm M.L. Catbagan W.S. Laciak R.J. Barnett D.H. Hebner C.M. Gaffield W. Walterhouse D. Iannaccone P. Bushman W. Dev. Biol. 2002; 249: 349-366Crossref PubMed Scopus (137) Google Scholar, Y. Dev. Biol. 2004; PubMed Scopus Google Scholar), to and in in the study that impaired lateral branching in the Klf6-deficient prostate an and loss of of Ptc, and for the of in prostate epithelial branching a study by Bushman and M.L. Catbagan W.S. Laciak R.J. Barnett D.H. Hebner C.M. Gaffield W. Walterhouse D. Iannaccone P. Bushman W. Dev. Biol. 2002; 249: 349-366Crossref PubMed Scopus (137) Google Scholar), a between prostate ductal and localized of Shh at the of prostate In addition, Shh prostate branching morphogenesis in FGF10 and BMP4 Y. Dev. Biol. 2004; PubMed Scopus Google Scholar). Shh the epithelial ductal FGF10 that stimulates epithelial cell growth (16Thomson A.A. Cunha G.R. Development. 1999; 126: 3693-3701PubMed Google BMP4 that inhibits epithelial cell growth (17Lamm M.L. Podlasek C.A. Barnett D.H. Lee J. Clemens J.Q. Hebner C.M. Bushman W. Dev. Biol. 2001; 232: 301-314Crossref PubMed Scopus (124) Google in the which in epithelial ductal branching Y. Dev. Biol. 2004; PubMed Scopus Google Scholar). In the that loss of Klf6 leads to Shh the epithelial ducts and and in the mesenchyme domain of pathway leads to an of BMP4 expression, in ductal branching. by and the and localized of Shh and BMP4 to branching Y. Dev. Biol. 2004; PubMed Scopus Google is reported to be a tumor suppressor that is in a large of prostate G. Friedman S.L. Martignetti J.A. J. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). our of as as to prostate C. B. J. S. M. J. R. A. D. G. M. M. F. J. de and The of tumor in the Klf6 be to other Klf family is that loss of Klf6 not be to prostate in the mouse and that of tumor be The Klf gene family is known to be for development in A.C. Pratt S.J. Vail B. Yan Y.I. Ho R.K. Johnson S.L. Postlethwait J.H. Zon L.I. Blood. 2001; 98: 1792-1801Crossref PubMed Scopus (92) Google Scholar). in a large number of J. M. 1999; Full Text Full Text PDF PubMed Scopus Google and play an role in the of cell differentiation A.C. Pratt S.J. Vail B. Yan Y.I. Ho R.K. Johnson S.L. Postlethwait J.H. Zon L.I. Blood. 2001; 98: 1792-1801Crossref PubMed Scopus (92) Google Scholar), cell B. D. A. R. F. PubMed Scopus Google Scholar, A.C. S.H. PubMed Scopus (127) Google Scholar), activation M.L. Science. PubMed Scopus Google Scholar), M.L. M.M. C. Dev. 11: PubMed Scopus Google Scholar), and J.A. C. E. 1999; PubMed Scopus Google Scholar). the prostate as a here for the first a role for Klf6 in prostate branching morphogenesis. Klf family has been to be for in the of leads to and of which in and in V. S. T. P. P. J. C. Dev. 2008; PubMed Scopus Google Scholar). In the Klf6 is known to be in the and J.A. J. 2001; PubMed Google Scholar), an that be a role in branching morphogenesis. loss of Klf6 is N. A. H. K. F. Ramirez F. G. Friedman S.L. Blood. 2006; PubMed Scopus Google Scholar), generated for Klf6 specifically in the The lateral branching in Klf6-deficient prostate by and a novel to that Klf6 a role in the epithelial and which in of The branching in the known as a which the of Klf6 the in epithelial and not prostatic function has been impaired in to be The branching in the prostate is the branching in the prostate distinct the prostate and In addition, the of the prostate is different the other prostate G.R. B. of Scholar, G.R. T. Donjacour A.A. B.A. J. Google Scholar). Although branching of the prostate and to the epithelium into the prostate is to be epithelium at the of the into the mesenchyme of the which is the the in the prostate has distinct the other prostate and as a of lateral and not as a of at the our and others the role of Shh in prostate branching (12Freestone S.H. Marker P. Grace O.C. Tomlinson D.C. Cunha G.R. Harnden P. Thomson A.A. Dev. Biol. 2003; 264: 352-362Crossref PubMed Scopus (128) Google Scholar, 13Wang B.E. Shou J. Ross S. Koeppen H. De Sauvage F.J. Gao W.Q. J. Biol. Chem. 2003; 278: 18506-18513Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 14Berman D.M. Desai N. Wang X. Karhadkar S.S. Reynon M. Abate-Shen C. Beachy P.A. Shen M.M. Dev. Biol. 2004; 267: 387-398Crossref PubMed Scopus (111) Google Scholar, 15Lamm M.L. Catbagan W.S. Laciak R.J. Barnett D.H. Hebner C.M. Gaffield W. Walterhouse D. Iannaccone P. Bushman W. Dev. Biol. 2002; 249: 349-366Crossref PubMed Scopus (137) Google Scholar, Y. Dev. Biol. 2004; PubMed Scopus Google Scholar), to and in in the study that impaired lateral branching in the Klf6-deficient prostate an and loss of of Ptc, and for the of in prostate epithelial branching a study by Bushman and M.L. Catbagan W.S. Laciak R.J. Barnett D.H. Hebner C.M. Gaffield W. Walterhouse D. Iannaccone P. Bushman W. Dev. Biol. 2002; 249: 349-366Crossref PubMed Scopus (137) Google Scholar), a between prostate ductal and localized of Shh at the of prostate In addition, Shh prostate branching morphogenesis in FGF10 and BMP4 Y. Dev. Biol. 2004; PubMed Scopus Google Scholar). Shh the epithelial ductal FGF10 that stimulates epithelial cell growth (16Thomson A.A. Cunha G.R. Development. 1999; 126: 3693-3701PubMed Google BMP4 that inhibits epithelial cell growth (17Lamm M.L. Podlasek C.A. Barnett D.H. Lee J. Clemens J.Q. Hebner C.M. Bushman W. Dev. Biol. 2001; 232: 301-314Crossref PubMed Scopus (124) Google in the which in epithelial ductal branching Y. Dev. Biol. 2004; PubMed Scopus Google Scholar). In the that loss of Klf6 leads to Shh the epithelial ducts and and in the mesenchyme domain of pathway leads to an of BMP4 expression, in ductal branching. by and the and localized of Shh and BMP4 to branching Y. Dev. Biol. 2004; PubMed Scopus Google Scholar). Klf6 is reported to be a tumor suppressor that is in a large of prostate G. Friedman S.L. Martignetti J.A. J. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). our of as as to prostate C. B. J. S. M. J. R. A. D. G. M. M. F. J. de and The of tumor in the Klf6 be to other Klf family is that loss of Klf6 not be to prostate in the mouse and that of tumor be We and for We and for the for of BMP4 in and for Klf6 prostate branching morphogenesis activation of the Shh of PDF
No takes yet. Share an insight, caveat, or question.
Leow et al. (2009) studied this question.
Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context: