Fibroblast Growth Factor-9 in Marsupial Testicular DevelopmentChung J.W.a, b · Pask A.J.a–c · Yu H.a, b · Renfree M.B.a, b
aAustralian Research Council Centre of Excellence in Kangaroo Genomics, and bDepartment of Zoology, University of Melbourne,Vic., Australia; cDepartment of Molecular and Cellular Biology, University of Connecticut, Storrs, Conn., USA
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FGF9 is a member of the fibroblast growth factor (FGF) family and is critical for early testicular development and germ cell survival in the mouse. Fgf9 reinforces the testis determinant Sox9 and antagonizes Wnt4, an ovarian factor. To determine whether FGF9 has a conserved role in the mammalian gonad, we examined its expression in the gonads of a marsupial, the tammar wallaby Macropus eugenii, and compared it to WNT4 expression. Marsupial FGF9 is highly conserved with orthologues from eutherian mammals, including humans. FGF9 protein was detected in both the testis and ovary before sexual differentiation, but it subsequently became sexually dimorphic during the period of testicular differentiation. The protein was specifically enriched in the seminiferous cords of the developing testis in the Sertoli and germ cells. FGF9 mRNA expression was upregulated in the tammar testis at the time of seminiferous cord formation and downregulated in the developing ovary in an opposite profile to that of marsupial WNT4. These observations suggest that FGF9 promotes male fate in the early gonad of marsupials through an antagonistic relationship with WNT4 as it does in eutherian mammals.
© 2011 S. Karger AG, Basel
- Alcorn GT, Robinson ES: Germ cell development in female pouch young of the tammar wallaby (Macropus eugenii). J Reprod Fertil 67:319–325 (1983).
- Barrios F, Filipponi D, Pellegrini M, Paronetto MP, Di Siena S, et al: Opposing effects of retinoic acid and FGF9 on Nanos2 expression and meiotic entry of mouse germ cells. J Cell Sci 123:871–880 (2010).
- Bininda-Emonds OR, Cardillo M, Jones KE, MacPhee RD, Beck RM, et al: The delayed rise of present-day mammals. Nature 446:507–512 (2007).
- Bowles J, Feng CW, Spiller C, Davidson TL, Jackson A, Koopman P: FGF9 suppresses meiosis and promotes male germ cell fate in mice. Dev Cell 19:440–449 (2010).
- Burgoyne PS, Thornhill AR, Boudrean SK, Darling SM, Bishop CE, Evans EP: The genetic basis of XX-XY differences present before gonadal sex differentiation in the mouse. Philos Trans R Soc Lond B Biol Sci 350:253–260 discussion 260–251 (1995).
Chen TM, Kuo PL, Hsu CH, Tsai SJ, Chen MJ, et al: Microsatellite in the 3′ untranslated region of human fibroblast growth factor 9 (FGF9) gene exhibits pleiotropic effect on modulating FGF9 protein expression. Hum Mutat 28:98 (2007).
- Colvin JS, Feldman B, Nadeau JH, Goldfarb M, Ornitz DM: Genomic organization and embryonic expression of the mouse fibroblast growth factor 9 gene. Dev Dyn 216:72–88 (1999).
- Colvin JS, White AC, Pratt SJ, Ornitz DM: Lung hypoplasia and neonatal death in Fgf9-null mice identify this gene as an essential regulator of lung mesenchyme. Development 128:2095–2106 (2001a).
- Colvin JS, Green RP, Schmahl J, Capel B, Ornitz DM: Male-to-female sex reversal in mice lacking fibroblast growth factor 9. Cell 104:875–889 (2001b).
- DiNapoli L, Batchvarov J, Capel B: FGF9 promotes survival of germ cells in the fetal testis. Development 133:1519–1527 (2006).
- Drummond AE, Tellbach M, Dyson M, Findlay JK: Fibroblast growth factor-9, a local regulator of ovarian function. Endocrinology 148:3711–3721 (2007).
- Foster JW, Brennan FE, Hampikian GK, Goodfellow PN, Sinclair AH, et al: Evolution of sex determination and the Y chromosome: SRY-related sequences in marsupials. Nature 359:531–533 (1992).
- Goldfarb M: Functions of fibroblast growth factors in vertebrate development. Cytokine Growth Factor Rev 7:311–325 (1996).
- Goldfarb M: Fibroblast growth factors homologous factors: evolution, structure and function. Cytokine Growth Factor Rev 16:215–220 (2005).
- Harry JL, Koopman P, Brennan FE, Graves JA, Renfree MB: Widespread expression of the testis-determining gene SRY in a marsupial. Nat Genet 11:347–349 (1995).
- Hiramatsu R, Harikae K, Tsunekawa N, Kurohmaru M, Matsuo I, Kanai Y: FGF signaling directs a center-to-pole expansion of tubulogenesis in mouse testis differentiation. Development 137:303–312 (2010).
- Itoh N, Ornitz DM: Evolution of the FGF and FGFR gene families. Trends Genet 20:563–569 (2004).
- Itoh N, Ornitz DM: Functional evolutionary history of the mouse Fgf gene family. Dev Dyn 237:18–27 (2008).
- Ji Q, Luo ZX, Yuan CX, Wible JR, Zhang JP, Georgi JA: The earliest known eutherian mammal. Nature 416:816–822 (2002).
- Kim Y, Capel B: Balancing the bipotential gonad between alternative organ fates: a new perspective on an old problem. Dev Dyn 235:2292–2300 (2006).
- Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, et al: Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol 4:e187 (2006).
- Luo ZX, Ji Q, Wible JR, Yuan CX: An early cretaceous tribosphenic mammal and metatherian evolution. Science 302:1934–1940 (2003).
- Miyakawa K, Hatsuzawa K, Kurokawa T, Asada M, Kuroiwa T, Imamura T: A hydrophobic region locating at the center of fibroblast growth factor-9 is crucial for its secretion. J Biol Chem 274:29352–29357 (1999).
- Nef S, Schaad O, Stallings NR, Cederroth CR, Pitetti JL, et al: Gene expression during sex determination reveals a robust female genetic program at the onset of ovarian development. Dev Biol 287:361–377 (2005).
- O’Shaughnessy PJ, Baker PJ, Monteiro A, Cassie S, Bhattacharya S, Fowler PA: Developmental changes in human fetal testicular cell numbers and messenger ribonucleic acid levels during the second trimester. J Clin Endocrinol Metab 92:4792–4801 (2007).
- O WS, Short RV, Renfree MB, Shaw G: Primary genetic control of somatic sexual differentiation in a mammal. Nature 331:716–717 (1988).
Ornitz DM, Itoh N: Fibroblast growth factors. Genome Biol 2:reviews3005.1–reviews3005.12 (2001).
- Ostrer H, Huang HY, Masch RJ, Shapiro E: A cellular study of human testis development. Sex Dev 1:286–292 (2007).
- Palmer SJ, Burgoyne PS: In situ analysis of fetal, prepuberal and adult XX-XY chimaeric mouse testes: Sertoli cells are predominantly, but not exclusively, XY. Development 112:265–268 (1991).
- Pask AJ, Harry JL, Graves JA, O’Neill RJ, Layfield SL, et al: SOX9 has both conserved and novel roles in marsupial sexual differentiation. Genesis 33:131–139 (2002).
- Pask AJ, Calatayud NE, Shaw G, Wood WM, Renfree MB: Oestrogen blocks the nuclear entry of SOX9 in the developing gonad of a marsupial mammal. BMC Biol 8:113 (2010).
Poole WE, Simms NG, Wood JT, Lubulwa M: Tables for age determination of the Kangaroo Island wallaby (tammar), Macropus eugenii, from body measurements, CSIRO Division of Wildlife and Ecology, vol Technical Memorandum number 32 (1991).
- Renfree MB: The composition of fetal fluids of the marsupial Macropus eugenii. Dev Biol 33:62–79 (1973).
Renfree MB: Sexual dimorphisms in the gonads and reproductive tracts of marsupial mammals; in Short RV, Balaban V (eds): The Differences Between the Sexes, pp 433–448 (Cambridge University Press, Cambridge 1994).
- Renfree MB, Tyndale-Biscoe CH: Intrauterine development after diapause in the marsupial Macropus eugenii. Dev Biol 32:28–40 (1973).
- Renfree MB, Short RV: Sex determination in marsupials: evidence for a marsupial-eutherian dichotomy. Philos Trans R Soc Lond B Biol Sci 322:41–53 (1988).
Renfree MB, Fletcher TP, Blanden DR, Lewis PR, Shaw G, et al: Physiological and behavioural events around the time of birth in macropodid marsupials; in Grigg G, Jarman P, Hume ID (eds): Kangaroos, Wallabies and Rat Kangaroos, pp 323–337 (Surrey Beatty & Sons Pty Ltd, Sydney 1989).
- Renfree MB, O WS, Short RV, Shaw G: Sexual differentiation of the urogenital system of the fetal and neonatal tammar wallaby, Macropus eugenii. Anat Embryol (Berl) 194:111–134 (1996).
Revest JM, DeMoerlooze L, Dickson C: Fibroblast growth factor 9 secretion is mediated by a non-cleaved amino-terminal signal sequence. J Biol Chem 275:8083–8090 (2000).
- Rhen T, Metzger K, Schroeder A, Woodward R: Expression of putative sex-determining genes during the thermosensitive period of gonad development in the snapping turtle, Chelydra serpentina. Sex Dev 1:255–270 (2007).
- Santos-Ocampo S, Colvin JS, Chellaiah A, Ornitz DM: Expression and biological activity of mouse fibroblast growth factor-9. J Biol Chem 271:1726–1731 (1996).
- Schmahl J, Kim Y, Colvin JS, Ornitz DM, Capel B: Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination. Development 131:3627–3636 (2004).
- Song J, Slack JM: XFGF-9: a new fibroblast growth factor from Xenopus embryos. Dev Dyn 206:427–436 (1996).
- Tamura K, Dudley J, Nei M, Kumar S: MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599 (2007).
- Willerton L, Smith RA, Russell D, Mackay S: Effects of FGF9 on embryonic Sertoli cell proliferation and testicular cord formation in the mouse. Int J Dev Biol 48:637–643 (2004).
- Yamamura Y, Aoyama S, Oshima Y, Kato T, Osawa N, Nakamura M: Molecular cloning and expression in gonad of Rana rugosaWT1 and Fgf9. Zoolog Sci 22:1045–1050 (2005).
- Yoshioka H, Ishimaru Y, Sugiyama N, Tsunekawa N, Noce T, et al: Mesonephric FGF signaling is associated with the development of sexually indifferent gonadal primordium in chick embryos. Dev Biol 280:150–161 (2005).
- Yu H, Pask AJ, Shaw G, Renfree MB: Differential expression of WNT4 in testicular and ovarian development in a marsupial. BMC Dev Biol 6:44 (2006).
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