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マウス胚尿生殖洞上皮を用いた初期前立腺発生におけるFGF10、WNT、レチノイン酸シグナルの機能解析

宇野, 亘 京都大学 DOI:10.14989/doctor.k24944

2023.09.25

概要

前立腺は哺乳類の生殖能力向上に寄与する前立腺液を分泌する雄
性生殖器官であり、胚発生においては膀胱直下の尿生殖洞(UGS)に
由来する。前立腺発生は精巣由来テストステロンを受容した UGS 間
充織 (UGM)から分泌された二次シグナルが UGS 上皮 (UGE)におい
て受容され、UGE で Nkx3.1 に代表される前立腺遺伝子の発現上昇が
起こる事によって開始される。その後上皮と間充織の間でシグナル
の相互作用が起こり、前立腺芽が形成される。先行研究において
UGS を用いた組織培養により、複数のシグナル因子が前立腺の発生
に重要である事が示されているが、UGM 由来シグナル因子の種類
が膨大であるため、前立腺芽形成に必要かつ十分な因子はこれまで
明瞭には判明していなかった。加えて、出芽が起きる前の“prebudding 期”の時点において遺伝子発現に雌雄間で差異が生じている
事が近年判明しているが、pre-budding 期の前立腺分化に関してはこ
れまでほとんど調べられていなかった。 ...

参考文献

Abashev, T.M., Metzler, M.A., Wright, D.M. and Sandell, L.L.

(2017) Retinoic acid signaling regulates Krt5 and Krt14

independently of stem cell markers in submandibular salivary

gland epithelium. Developmental Dynamics. 246. 135-147.

Abler, L.L., Keil, K.P., Mehta, V., Joshi, P.S., Schmitz, C.T. and

Vezina, C.M. (2011) A high-resolution molecular atlas of the fetal

mouse lower urogenital tract. Developmental Dynamics. 240.

2364-2377.

Allgeier, S.H., Lin, T.M., Vezina, C.M., Moore, R.W., Fritz, W.A.,

Chiu, S.Y., Zhang, C. and Peterson, R.E. (2008) WNT5A selectively

inhibits mouse ventral prostate development. Developmental

Biology. 324. 10-17.

Bhatia-Gaur, R., Donjacour, A.A., Sciavolino, P.J., Kim, M., Desai,

N., Young, P., Norton, C.R., Gridley, T., Cardiff, R.D., Cunha, G.R.,

Abate-Shen, C. and Shen, M.M. (1999) Roles for Nkx3.1 in prostate

development and cancer. Genes & Development. 13. 966-977.

Boutin, E.L., Battle, E. and Cunha, G.R. (1991) The response of

female urogenital tract epithelia to mesenchymal inductors is

restricted by the germ layer origin of the epithelium: prostatic

inductions. Differentiation. 48. 99-105.

Brent, A.E. and Tabin, C.J. (2004) FGF acts directly on the somitic

tendon progenitors through the Ets transcription factors Pea3 and

Erm to regulate scleraxis expression. Developmental. 131. 38853896.

Bryant, S. L., Francis, J. C., Lokody, I. B., Wang, H., Risbridger, G.

P., Loveland, K. L. and Swain, A. (2014) Sex specific retinoic acid

signaling is required for the initiation of urogenital sinus bud

development. Developmental Biology. 395. 209-217.

68

Cook, C., Vezina, C.M., Allgeier, S.H., Shaw, A., Yu, M., Peterson,

R.E. and Bushman, W. (2007) Noggin is required for normal lobe

patterning and ductal budding in the mouse prostate.

Developmental Biology. 312. 217-230.

Crocoll, A., Zhu, C.C., Cato, A.C.B. and Blum, M. (1998)

Expression of androgen receptor mRNA during mouse

embryogenesis. Mech Dev. 72. 175–178.

Cunha, G.R. (1975) Age-Dependent Loss of Sensitivity of Female

Urogenital Sinus to Androgenic Conditions as a Function of the

Epithelial-Stromal Interaction in Mice. Endocrinology. 97. 665-673.

Cunha, G.R. and Lung, B. (1978) The possible influence of

temporal factors in androgenic responsiveness of urogenital tissue

recombinants from wild-type and androgen-insensitive (Tfm) mice.

Journal of Experimental Zoology. 205. 181-193.

Cunha, G.R., Fujii, H., Neubauner, B.L., Shannon, J.M., Sawyer,

L. and Reese, B.A. (1983) Epithelial-mesenchymal interactions in

prostatic development. I. Morphological observations of prostatic

induction by urogenital sinus mesenchyme in epithelium of the

adult rodent urinary bladder. Journal of Cell Biology. 96. 16621670.

Cunha, G.R., Vezina, C.M., Isaacson, D., Ricke, W.A., Timms, B.G.,

Cao, M., Franco, O. and Baskin, L.S. (2018) Development of the

human prostate. Differentiation. 103. 24-45.

Donjacour, A.A. and Cunha, G.R. (1993) Assessment of prostatic

protein secretion in tissue recombinants made of urogenital sinus

mesenchyme and urothelium from normal or androgen-insensitive

mice. Endocrinology. 132. 2342-2350.

Donjacour, A.A., Thomson, A.A. and Cunha, G.R. (2003) FGF-10

69

plays an essential role in the growth of the fetal prostate.

Developmental Biology. 261, 39-54.

Franklin, R. B., Milon, B., Feng, P. and Costello, L. C. (2005) Zinc

and zinc transporters in normal prostate and the pathogenesis of

prostate cancer. Frontiers in Bioscience. 10. 2230–2239.

Gandhi, D., Molotkov, A., Batourina, E., Schneider, K., Dan, H.,

Reiley, M., Laufer, E., Metzger, D., Liang, F., Liao, Y., Sun, T.T.,

Aronow, B., Rosen, R., Mauney, J., Adam, R., Rosselot, C., Van

Batavia, J., McMahon, A., McMahon, J., Guo, J.J. and Mendelsohn,

C. (2013) Retinoid signaling in progenitors controls specification

and regeneration of the urothelium. Developmental Cell. 26. 469482.

Georgas, K.M., Armstrong, J., Keast, J.R., Larkins, C.E., McHugh,

K.M., Southard-Smith, E.M., Cohn, M.J., Batourina, E., Dan, H.,

Schneider, K., Buehler, D.P., Wiese, C.B., Brennan, J., Davies, J.A.,

Harding, S.D., Baldock, R.A., Little, M.H., Vezina, C.M. and

Mendelsohn, C. (2015) An illustrated anatomical ontology of the

developing mouse lower urogenital tract. Development

(Cambridge). 142. 1893–1908.

Ghosh, S., Lau, H., Simons, B. W., Powell, J. D., Meyers, D. J., De

Marzo, A. M., Berman, D. M. and Lotan, T. L. (2011) PI3K/mTOR

signaling regulates prostatic branching morphogenesis.

Developmental Biology. 360. 329-342.

Habuka, M., Fagerberg, L., Hallström, B.M., Pontén, F.,

Yamamoto, T. and Uhlen, M. (2015) The urinary bladder

transcriptome and proteome defined by transcriptomics and

antibody-based profiling. PLoS ONE. 10. e0145301.

Haraguchi, R., Suzuki, K., Murakami, R., Sakai, M., Kamikawa,

M., Kengaku, M., Sekine, K., Kawano, H., Kato, S., Ueno, N. and

Yamada, G. (2000) Molecular analysis of external genitalia

70

formation: the role of fibroblast growth factor (Fgf) genes during

genital tubercle formation. Development. 127. 2471–2479.

Huang, Y.C., Chen, F. and Li, X. (2016) Clarification of mammalian

cloacal morphogenesis using high-resolution episcopic microscopy.

Developmental Biology. 409. 106–113.

Huang, Z., Hurley, P.J., Simons, B.W., Marchionni, L., Berman,

D.M., Ross, A.E. and Schaeffer, E.M. (2012) Sox9 is required for

prostate development and prostate cancer initiation. Oncotarget.

3. 651–663.

Joseph, D.B., Henry, G.H., Malewska, A., Iqbal, N.S., Ruetten,

H.M., Turco, A.E., Abler, L.L., Sandhu, S.K., Cadena, M.T.,

Malladi, V.S., Reese, J.C., Mauck, R.J., Gahan, J.C., Hutchinson,

R.C., Roehrborn, C.G., Baker, L.A., Vezina, C.M. and Strand, D.W.

(2020) Urethral luminal epithelia are castration-insensitive cells

of the proximal prostate. Prostate. 80. 872-884.

Keil, K.P., Mehta, V., Abler, L.L., Joshi, P.S., Schmitz, C.T. and

Vezina, C.M. (2012a) Visualization and quantification of mouse

prostate development by in situ hybridization. Differentiation. 84.

232-239.

Keil K.P., Mehta, V., Branam, A.M., Abler, L.L., Buresh-Stiemke,

R.A., Joshi, P.S., Schmitz, C.T., Marker, P.C. and Vezina, C.M.

(2012b) Wnt inhibitory factor 1 (Wif1) is regulated by androgens

and enhances androgen-dependent prostate development.

Endocrinology. 153. 6091-6103.

Keil, K.P., Abler, L.L., Laporta, J., Altmann, H.M., Yang, B.,

Jarrard, D.F., Hernandez, L.L. and Vezina, C.M. (2014) Androgen

receptor DNA methylation regulates the timing and androgen

sensitivity of mouse prostate ductal development. Developmental

Biology. 396. 237–245

71

Kruithof-de Julio, M., Shibata, M., Desai, N., Reynon, M., Halili,

M.V., Hu, Y.P., Price, S.M., Abate-Shen, C. and Shen, M.M. (2013).

Canonical Wnt signaling regulates Nkx3.1 expression and luminal

epithelial differentiation during prostate organogenesis.

Developmental Dynamics. 242. 1160–1171.

Kuslak, S.L. and Marker, P.C. (2007) Fibroblast growth factor

receptor signaling through MEK-ERK is required for prostate bud

induction. Differentiation. 75. 638-651.

Kwon, O.J., Zhang, L. and Xin, L. (2016) Stem Cell Antigen-1

Identifies a Distinct Androgen-Independent Murine Prostatic

Luminal Cell Lineage with Bipotent Potential. Stem Cells 34. 191–

202.

Kwon, O.J., Choi, J.M., Zhang, L., Jia, D., Li, Z., Zhang, Y., Jung,

S.Y., Creighton, C.J. and Xin, L. (2020) The Sca-1+ and Sca-1−

mouse prostatic luminal cell lineages are independently sustained.

Stem Cells. 38. 1479–1491.

Lamm, M.L., Podlasek, C.A., Barnett, D.H., Lee, J., Clemens, J.Q.,

Hebner, C.M. and Bushman, W. (2001) Mesenchymal factor bone

morphogenetic protein 4 restricts ductal budding and branching

morphogenesis in the developing prostate. Developmental Biology.

232. 301–314.

Lee, D.H., Olson, A.W., Wang, J., Kim, W.K., Mi, J., Zeng, H., Le,

V., Aldahl, J., Hiroto, A., Wu, X. and Sun, Z. (2021) Androgen

action in cell fate and communication during prostate

development at single-cell resolution. Development. 148.

dev196048

Mao, J., McGlinn, E., Huang, P., Tabin, C.J. and McMahon, A.P.

(2009) Fgf-dependent Etv4/5 activity is required for posterior

restriction of Sonic Hedgehog and promoting outgrowth of the

vertebrate limb. Developmental Cell. 16. 600-606.

72

Matuo, Y., Nishi, N., Muguruma, Y., Yoshitake, Y., Kurata, N. and

Wada, F. (1985) Localization of prostatic basic protein (“probasin”)

in the rat prostates by use of monoclonal antibody. Biochemical

and Biophysical Research Communications. 130. 293–300.

Mauney, J.R., Ramachandran, A., Yu, R.N., Daley, G.Q., Adam,

R.M. and Estrada, C.R. (2010) All-trans retinoic acid directs

urothelial specification of murine embryonic stem cells via

GATA4/6 signaling mechanisms. PLoS ONE. 5. e11513.

Mehta, V., Schmitz, C.T., Keil, K.P., Joshi, P.S., Abler, L.L., Lin, T.,

Taketo, M.M., Sun, X. and Vezina, C.M. (2013) Beta-catenin

(CTNNB1) induces Bmp expression in urogenital sinus epithelium

and participates in prostatic bud initiation and patterning.

Developmental Biology. 376. 125–135.

Mevel, R., Steiner, I., Mason, S., Galbraith, L.C.A., Patel, R.,

Fadlullah, M.Z.H., Ahmad, I., Leung, H.Y., Oliveira, P., Blyth, K.,

Baena, E. and Lacaud, G. (2020) Runx1 marks a luminal

castration-resistant lineage established at the onset of prostate

development. Elife 9, 1–27.

Mizuno, T and Saito, M. (1996) Induction of prostatic buds in the

urogenital sinus in Tfm mouse embyos without androgen receptors.

C R Seances Soc Biol Fil. 190. 497-501

Nowotschin, S., Ferrer-Vaquer, A. and Hadjantonakis, A.K. (2010)

Imaging mouse development with confocal time-lapse microscopy.

Methods in Enzymology. 476. 351–377.

Pampalakis G. and Sotiropoulou G. (2007) Tissue kallikrein

proteolytic cascade pathways in normal physiology and cancer.

Biochimica et biophysica acta. 1776. 22–31.

Perriton, C.L., Powles, N., Chiang, C., Maconochie, M.K. and Cohn,

73

M.J. (2002) Sonic hedgehog signaling from the urethral epithelium

controls external genital development. Developmental Biology.

247. 26–46.

Pointis, G., Latreille, M.T., Mignot, T.M., Janssens, Y. and Cedard,

L. (1979) Regulation of testosterone synthesis in the fetal mouse

testis. Journal of Steroid Biochemistry. 11. 1609-1612.

Roux, M., Bouchard, M. and Kmita, M. (2019) Multifaceted

Hoxa13 function in urogenital development underlies the HandFoot-Genital Syndrome. Hum Mol Genet. 28. 1671–1681.

Saito, M and Mizuno, T. (1997) Prostatic bud induction by brief

treatment with growth factors. C R Seances Soc Biol Fil. 191. 261265

Seifert, A.W., Harfe, B.D. and Cohn, M.J. (2008) Cell lineage

analysis demonstrates an endodermal origin of the distal urethra

and perineum. Developmental Biology. 318. 143–152.

Simons, B.W., Hurley, P.J., Huang, Z., Ross, A.E., Miller, R.,

Marchionni, L., Berman, D.M. and Schaeffer, E.M. (2012) Wnt

signaling though beta-catenin is required for prostate lineage

specification. Developmental Biology. 371. 246–255.

Thielen, J.L., Volzing, K.G., Collier, L.S., Green, L.E., Largaespada,

D.A. and Marker, P.C. (2007) Markers of prostate region-specific

epithelial identity define anatomical locations in the mouse

prostate that are molecularly similar to human prostate cancers.

Differentiation. 75. 49-61.

Thomsen, M. K., Butler, C. M., Shen, M. M. and Swain, A. (2008)

Sox9 is required for prostate development. Developmental Biology.

316. 302–311.

Thomson, A.A. and Cunha, G.R. (1999) Prostatic growth and

74

development are regulated by FGF10. Development. 126. 36933701.

Toivanen, R. and Shen, M.M. (2017) Prostate organogenesis: tissue

induction, hormonal regulation and cell type specification.

Development. 144. 1382-1398.

Verze, P., Cai, T and Lorenzetti, S. (2016) The role of the prostate

in male fertility, health and disease. Nature Reviews Urology. 13.

379-386.

Vezina C.M., Allgeier S.H., Fritz W.A., Moore, R. W., Strerath, M.,

Bushman, W. and Peterson, R. E. (2008) Retinoic acid induces

prostatic bud formation. Developmental Dynamics. 237. 1321–

1333.

Yeh, S., Tsai, M.Y., Xu, Q., Mu, X.M., Lardy, H., Huang, K.E., Lin,

H., Yeh, S.D., Altuwaijri, S., Zhou, X., Xing, L., Boyce, B. F., Hung,

M. C., Zhang, S., Gan, L. and Chang, C. (2002) Generation and

characterization of androgen receptor knockout (ARKO) mice: An

in vivo model for the study of androgen functions in selective

tissues. Proceedings of the National Academy of Sciences USA. 99.

13498-13503.

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謝辞

本研究の遂行および論文の執筆にあたり、終始厚いご指導を賜り

ました京都大学大学院 生命科学研究科 高次生命科学専攻 分子病態

学分野 高里 実 准教授に厚く御礼申し上げます。実験に際し、理化

学研究所 生命機能科学研究センター ヒト器官形成研究チーム 研究

員の Filip Wymeersch 博士、リサーチ・アソシエイトの尾藤 和浩さ

んをはじめとするヒト器官形成研究チームの皆様には、研究に対す

る姿勢、実験データに対する解釈および考察の方法等に関し、多大

なご助言、ご協力をいただきました。また、籔内 研佑さんには腎被

膜下移植の方法等に関し、丁寧なご指導をいただきました。ここに

感謝の意を表します。

最後に、本研究にあたり多大な支援をいただきました家族に心か

ら感謝を申し上げます。

本研究は理研の大学院生リサーチ・アソシエイト制度の下での成

果です。

本学位論文は以下の学術論文の内容に基づいて書かれたものである。

Wataru Uno, Kazuhiro Ofuji, Filip J. Wymeersch and Minoru

Takasato

In vitro induction of prostate buds from murine urogenital

76

epithelium in the absence of mesenchymal cells

Developmental Biology, 498, 49-60, 2023

77

...

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