Abstract
During embryonic development, ovarian somatic cells embark on a course that is separate from male somatic cells and from indifferent precursor cells. While the former aspect of ovarian development is well known, the latter has not received much attention until recently. This review attempts to integrate the most recent work regarding the differentiation of ovarian somatic cells. The discussion of the parallel development of the testis is limited to the key differences only. Similarly, germ cell development will be introduced only inasmuch as it becomes necessary to draw attention to a particular aspect of the somatic component differentiation. Finally, while postnatal ovarian development and folliculogenesis undoubtedly provide the ultimate morphological and functional fitness tests for the ovarian somatic cells, postnatal phenotypes will be only referred to when they have already been connected to genes that are expressed during embryogenesis.
Journal Section:
Editor's choice
References
1.
Albrecht KH, Eicher EM: Evidence that Sry is expressed in pre-Sertoli cells and Sertoli and granulosa cells have a common precursor. Dev Biol 240:92–107 (2001).
[PubMed]
2.
Arboleda VA, Vilain E: The evolution of the search for novel genes in mammalian sex determination: from mice to men. Mol Genet Metab 104:67–71 (2011).
[PubMed]
3.
Bafico A, Liu G, Yaniv A, Gazit A, Aaronson SA: Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat Cell Biol 3:683–686 (2001).
[PubMed]
4.
Barrionuevo F, Bagheri-Fam S, Klattig J, Kist R, Taketo MM, et al: Homozygous inactivation of Sox9 causes complete XY sex reversal in mice. Biol Reprod 74:195–201 (2006).
[PubMed]
5.
Barrionuevo F, Georg I, Scherthan H, Lecureuil C, Guillou F, et al: Testis cord differentiation after the sex determination stage is independent of Sox9 but fails in the combined absence of Sox9 and Sox8. Dev Biol 327:301–312 (2009).
[PubMed]
6.
Bernard P, Harley VR: Wnt4 action in gonadal development and sex determination. Int J Biochem Cell Biol 39:31–43 (2007).
[PubMed]
7.
Beverdam A, Koopman P: Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes. Hum Mol Genet 15:417–431 (2006).
[PubMed]
8.
Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ: A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46,XX woman. N Engl J Med 351:792–798 (2004).
[PubMed]
9.
Biason-Lauber A, De Filippo G, Konrad D, Scarano G, Nazzaro A, Schoenle EJ: WNT4 deficiency – a clinical phenotype distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome: a case report. Hum Reprod 22:224–229 (2007).
[PubMed]
10.
Bingham NC, Verma-Kurvari S, Parada LF, Parker KL: Development of a steroidogenic factor 1/Cre transgenic mouse line. Genesis 44:419–424 (2006).
[PubMed]
11.
Binnerts ME, Kim KA, Bright JM, Patel SM, Tran K, et al: R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proc Natl Acad Sci USA 104:14700–14705 (2007).
[PubMed]
12.
Bishop CE, Whitworth DJ, Qin Y, Agoulnik AI, Agoulnik IU, et al: A transgenic insertion upstream of Sox9 is associated with dominant XX sex reversal in the mouse. Nat Genet 26:490–494 (1999).
13.
Brault V, Moore R, Kutsch S, Ishibashi M, Rowitch DH, et al: Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development 128:1253–1264 (2001).
[PubMed]
14.
Brennan J, Capel B: One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nat Rev Genet 5:509–521 (2004).
[PubMed]
15.
Britt KL, Stanton PG, Misso M, Simpson ER, Findlay JK: The effects of estrogen on the expression of genes underlying the differentiation of somatic cells in the murine gonad. Endocrinology 145:3950–3960 (2004).
[PubMed]
16.
Burgoyne PS: Role of mammalian Y chromosome in sex determination. Philos Trans R Soc Lond B Biol Sci 322:63–72 (1988).
[PubMed]
17.
Burgoyne PS, Buehr M, McLaren A: XY follicle cells in ovaries of XX-XY female mouse chimaeras. Development 104:683–688 (1988).
[PubMed]
18.
Buscara L, Montazer-Torbati F, Chadi S, Auguste A, Laubier J, et al: Goat RSPO1 over-expression rescues sex-reversal in Rspo1-knockout XX mice but does not perturb testis differentiation in XY or sex-reversed XX mice. Transgenic Res 18:649–654 (2009).
[PubMed]
19.
Byskov AG: Differentiation of mammalian embryonic gonad. Physiol Rev 66:71–117. (1986).
[PubMed]
20.
Byskov AG, Nielsen M: Ontogeny of the mammalian ovary, in Trounson AO, Gosden RG (eds): Biology and Pathology of the Oocyte, pp 13–28 (Cambridge University Press, New York 2003).
21.
Capel B: The battle of the sexes. Mech Dev 92:89–103 (2000).
[PubMed]
22.
Capel B: R-spondin1 tips the balance in sex determination. Nat Genet 38:1233–1234 (2006).
[PubMed]
23.
Carmon KS, Gong X, Lin Q, Thomas A, Liu Q: R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proc Natl Acad Sci USA 108:11452–11457 (2011).
[PubMed]
24.
Cederroth CR, Pitetti JL, Papaioannou MD, Nef S: Genetic programs that regulate testicular and ovarian development. Mol Cell Endocrinol 265–266:3–9 (2007).
[PubMed]
25.
Chaboissier MC, Kobayashi A, Vidal VI, Lutzkendorf S, van de Kant HJ, et al: Functional analysis of Sox8 and Sox9 during sex determination in the mouse. Development 131:1891–1901 (2004).
[PubMed]
26.
Chang H, Gao F, Guillou F, Taketo MM, Huff V, Behringer RR: Wt1 negatively regulates beta-catenin signaling during testis development. Development 135:1875–1885 (2008).
[PubMed]
27.
Chassot AA, Ranc F, Gregoire EP, Roepers-Gajadien HL, Taketo MM, et al: Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet 17:1264–1277 (2008).
[PubMed]
28.
Clevers H: Wnt/beta-catenin signaling in development and disease. Cell 127:469–480 (2006).
[PubMed]
29.
Combes AN, Spiller C, Koopman P: Sex determination and gonadal development; in Verlhac MH, Villeneuve A (eds): Oogenesis: The Universal Process, pp 27–79 (John Wiley & Sons, Ltd, Chichester 2010).
30.
Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, et al: The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nat Genet 27:159–166 (2001).
[PubMed]
31.
DasGupta R, Fuchs E: Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development 126:4557–4568 (1999).
[PubMed]
32.
de Lau W, Barker N, Low TY, Koo BK, Li VS, et al: LGR5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476:293–297 (2011).
[PubMed]
33.
Dupont S, Krust A, Gansmuller A, Dierich A, Chambon P, Mark M: Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes. Development 127:4277–4291 (2000).
[PubMed]
34.
Dupont S, Dennefeld C, Krust A, Chambon P, Mark M: Expression of Sox9 in granulosa cells lacking the estrogen receptors, ERalpha and ERbeta. Dev Dyn 226:103–106 (2003).
35.
Edson MA, Nagaraja AK, Matzuk MM: The mammalian ovary: from genesis to revelation. Endocr Rev 30:624–712 (2009).
[PubMed]
36.
Eicher EM, Washburn LL: Inherited sex reversal in mice: identification of a new primary sex-determining gene. J Exp Zool 228:297–304 (1983).
[PubMed]
37.
Eicher EM, Washburn LL: Genetic control of primary sex determination in mice. Annu Rev Genet 20:327–360 (1986).
[PubMed]
38.
Eicher EM, Washburn LL, Whitney JB 3rd, Morrow KE: Mus poschiavinus Y chromosome in the C57BL/6J murine genome causes sex reversal. Science 217:535–537 (1982).
[PubMed]
39.
Elejalde BR, Opitz JM, de Elejalde MM, Gilbert EF, Abellera M, et al: Tandem dup (1p) within the short arm of chromosome 1 in a child with ambiguous genitalia and multiple congenital anomalies. Am J Med Genet 17:723–730 (1984).
[PubMed]
40.
Garcia-Ortiz JE, Pelosi E, Omari S, Nedorezov T, Piao Y, et al: Foxl2 functions in sex determination and histogenesis throughout mouse ovary development. BMC Dev Biol 9:36 (2009).
[PubMed]
41.
Gibbons C, Dackor R, Dunworth W, Fritz-Six K, Caron KM: Receptor activity-modifying proteins: RAMPing up adrenomedullin signaling. Mol Endocrinol 21:783–796 (2007).
[PubMed]
42.
Glinka A, Dolde C, Kirsch N, Huang YL, Kazanskaya O, et al: LGR4 and LGR5 are R-spondin receptors mediating Wnt/beta-catenin and Wnt/PCP signalling. EMBO Rep 12:1055–1061 (2011).
[PubMed]
43.
Gondos B, Zamboni L: Ovarian development: the functional importance of germ cell interconnections. Fertil Steril 20:176–189 (1969).
[PubMed]
44.
Goodfellow PN, Darling SM: Genetics of sex determination in man and mouse. Development 102:251–258 (1988).
[PubMed]
45.
Goodfellow PN, Lovell BR: SRY and sex determination in mammals. Annu Rev Genet 27:71–92 (1993).
[PubMed]
46.
Grigoryan T, Wend P, Klaus A, Birchmeier W: Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of beta-catenin in mice. Genes Dev 22:2308–2341 (2008).
[PubMed]
47.
Gubbay J, Collignon J, Koopman P, Capel B, Economou A, et al: A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature 346:245–250 (1990).
[PubMed]
48.
Hatano O, Takakusu A, Nomura M, Morohashi K: Identical origin of adrenal cortex and gonad revealed by expression profiles of Ad4BP/SF-1. Genes Cells 1:663–671 (1996).
[PubMed]
49.
Heikkila M, Peltoketo H, Leppaluoto J, Ilves M, Vuolteenaho O, Vainio S: Wnt4 deficiency alters mouse adrenal cortex function, reducing aldosterone production. Endocrinology 143:4358–4365 (2002).
[PubMed]
50.
Hong X, Luense LJ, McGinnis LK, Nothnick WB, Christenson LK: Dicer1 is essential for female fertility and normal development of the female reproductive system. Endocrinology 149:6207–6212 (2008).
[PubMed]
51.
Huang CC, Yao HH: Inactivation of Dicer1 in Steroidogenic Factor 1-positive cells reveals tissue-specific requirement for Dicer1 in adrenal, testis, and ovary. BMC Dev Biol 10:66 (2010).
[PubMed]
52.
Huang H, He X: Wnt/beta-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol 20:119–125 (2008).
[PubMed]
53.
Ito M, Yokouchi K, Yoshida K, Kano K, Naito K, et al: Investigation of the fate of Sry-expressing cells using an in vivo Cre/loxP system. Dev Growth Differ 48:41–47 (2006).
[PubMed]
54.
Jeays-Ward K, Hoyle C, Brennan J, Dandonneau M, Alldus G, et al: Endothelial and steroidogenic cell migration are regulated by WNT4 in the developing mammalian gonad. Development 130:3663–3670 (2003).
[PubMed]
55.
Jimenez R: Ovarian organogenesis in mammals: mice cannot tell us everything. Sex Dev 3:291–301 (2009).
[PubMed]
56.
Jordan BK, Mohammed M, Ching ST, Delot E, Chen XN, et al: Up-regulation of WNT4 signaling and dosage-sensitive sex reversal in humans. Am J Hum Genet 68:1102–1109 (2001).
[PubMed]
57.
Jordan BK, Shen JH, Olaso R, Ingraham HA, Vilain E: Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy. Proc Natl Acad Sci USA 100:10866–10871 (2003).
[PubMed]
58.
Jorgensen JS, Gao L: Irx3 is differentially up-regulated in female gonads during sex determination. Gene Expr Patterns 5:756–762 (2005).
[PubMed]
59.
Jost A: A new look at the mechanisms controlling sex differentiation in mammals. Johns Hopkins Med J 130:38–53 (1972).
[PubMed]
60.
Kashimada K, Pelosi E, Chen H, Schlessinger D, Wilhelm D, Koopman P: FOXL2 and BMP2 act cooperatively to regulate follistatin gene expression during ovarian development. Endocrinology 152:272–280 (2011).
[PubMed]
61.
Katoh M: WNT/PCP signaling pathway and human cancer (review). Oncol Rep 14:1583–1588 (2005).
[PubMed]
62.
Kazanskaya O, Glinka A, del Barco Barrantes I, Stannek P, Niehrs C, Wu W: R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis. Dev Cell 7:525–534 (2004).
[PubMed]
63.
Kikuchi A, Yamamoto H, Kishida S: Multiplicity of the interactions of Wnt proteins and their receptors. Cell Signal 19:659–671 (2007).
[PubMed]
64.
Kim KA, Kakitani M, Zhao J, Oshima T, Tang T, et al: Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science 309:1256–1259 (2005).
[PubMed]
65.
Kim KA, Zhao J, Andarmani S, Kakitani M, Oshima T, et al: R-Spondin proteins: a novel link to beta-catenin activation. Cell Cycle 5:23–26 (2006).
[PubMed]
66.
Kim KA, Wagle M, Tran K, Zhan X, Dixon MA, et al: R-Spondin family members regulate the Wnt pathway by a common mechanism. Mol Biol Cell 19:2588–2596 (2008).
[PubMed]
67.
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).
[PubMed]
68.
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).
[PubMed]
69.
Kimura F, Sidis Y, Bonomi L, Xia Y, Schneyer A: The follistatin-288 isoform alone is sufficient for survival but not for normal fertility in mice. Endocrinology 151:1310–1319 (2010).
[PubMed]
70.
Kimura F, Bonomi LM, Schneyer AL: Follistatin regulates germ cell nest breakdown and primordial follicle formation. Endocrinology 152:697–706 (2011).
[PubMed]
71.
Kocer A, Pinheiro I, Pannetier M, Renault L, Parma P, et al: R-spondin1 and FOXL2 act into two distinct cellular types during goat ovarian differentiation. BMC Dev Biol 8:36 (2008).
[PubMed]
72.
Kohn AD, Moon RT: Wnt and calcium signaling: beta-catenin-independent pathways. Cell Calcium 38:439–446 (2005).
[PubMed]
73.
Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell BR: Male development of chromosomally female mice transgenic for Sry. Nature 351:117–121 (1991).
[PubMed]
74.
Lee HJ, Pazin DE, Kahlon RS, Correa SM, Albrecht KH: Novel markers of early ovarian pre-granulosa cells are expressed in an Sry-like pattern. Dev Dyn 238:812–825 (2008).
75.
Lei L, Jin S, Gonzalez G, Behringer RR, Woodruff TK: The regulatory role of Dicer in folliculogenesis in mice. Mol Cell Endocrinol 315:63–73 (2010).
[PubMed]
76.
Liu CF, Bingham N, Parker K, Yao HH: Sex-specific roles of beta-catenin in mouse gonadal development. Hum Mol Genet 18:405–417 (2009).
[PubMed]
77.
Liu CF, Liu C, Yao HH: Building pathways for ovary organogenesis in the mouse embryo. Curr Top Dev Biol 90:263–290 (2010).
[PubMed]
78.
Loffler KA, Zarkower D, Koopman P: Etiology of ovarian failure in blepharophimosis ptosis epicanthus inversus syndrome: FOXL2 is a conserved, early-acting gene in vertebrate ovarian development. Endocrinology 144:3237–3243 (2003).
[PubMed]
79.
Ma Q, Zhou B, Pu WT: Reassessment of Isl1 and Nkx2–5 cardiac fate maps using a Gata4-based reporter of Cre activity. Dev Biol 323:98–104 (2008).
[PubMed]
80.
Maatouk DM, DiNapoli L, Alvers A, Parker KL, Taketo MM, Capel B: Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal. Hum Mol Genet 17:2949–2955 (2008).
[PubMed]
81.
Mandel H, Shemer R, Borochowitz ZU, Okopnik M, Knopf C, et al: SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4. Am J Hum Genet 82:39–47 (2008).
[PubMed]
82.
Manuylov NL, Smagulova FO, Leach L, Tevosian SG: Ovarian development in mice requires the GATA4-FOG2 transcription complex. Development 135:3731–3743 (2008).
[PubMed]
83.
Mao B, Wu W, Li Y, Hoppe D, Stannek P, et al: LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature 411:321–325 (2001).
[PubMed]
84.
Mao B, Wu W, Davidson G, Marhold J, Li M, et al: Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature 417:664–667 (2002).
[PubMed]
85.
Matson CK, Murphy MW, Sarver AL, Griswold MD, Bardwell VJ, Zarkower D: DMRT1 prevents female reprogramming in the postnatal mammalian testis. Nature 476:101–104 (2011).
[PubMed]
86.
McElreavey K, Vilain E, Abbas N, Herskowitz I, Fellous M: A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development. Proc Natl Acad Sci USA 90:3368–3372 (1993).
[PubMed]
87.
McLaren A: Development of the mammalian gonad: the fate of the supporting cell lineage. Bioessays 13:151–156 (1991).
[PubMed]
88.
McLaren A, Southee D: Entry of mouse embryonic germ cells into meiosis. Dev Biol 187:107–113 (1997).
[PubMed]
89.
Menke DB, Page DC: Sexually dimorphic gene expression in the developing mouse gonad. Gene Expr Patterns 2:359–367 (2002).
[PubMed]
90.
Menke DB, Koubova J, Page DC: Sexual differentiation of germ cells in XX mouse gonads occurs in an anterior-to-posterior wave. Dev Biol 262:303–312 (2003).
[PubMed]
91.
Mikels AJ, Nusse R: Purified WNT5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol 4:e115 (2006).
[PubMed]
92.
Miyanaga K, Shimasaki S: Structural and functional characterization of the rat follistatin (activin-binding protein) gene promoter. Mol Cell Endocrinol 92:99–109 (1993).
[PubMed]
93.
Mizusaki H, Kawabe K, Mukai T, Ariyoshi E, Kasahara M, et al: Dax1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1) gene transcription is regulated by Wnt4 in the female developing gonad. Mol Endocrinol 17:507–519 (2003).
[PubMed]
94.
Molkentin JD: The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression. J Biol Chem 275:38949–38952 (2000).
[PubMed]
95.
Morceau F, Schnekenburger M, Dicato M, Diederich M: GATA-1: friends, brothers, and coworkers. Ann N Y Acad Sci 1030:537–554 (2004).
[PubMed]
96.
Mork L, Maatouk DM, McMahon JA, Guo JJ, Zhang P, et al: Temporal differences in granulosa cell specification in the ovary reflect distinct follicle fates in mice. Biol Reprod 86:37 (2011).
97.
Munger SC, Aylor DL, Syed HA, Magwene PM, Threadgill DW, Capel B: Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal. Genes Dev 23:2521–2536 (2009).
[PubMed]
98.
Nagaraja AK, Andreu-Vieyra C, Franco HL, Ma L, Chen R, et al: Deletion of Dicer in somatic cells of the female reproductive tract causes sterility. Mol Endocrinol 22:2336–2352 (2008).
[PubMed]
99.
Nam JS, Turcotte TJ, Smith PF, Choi S, Yoon JK: Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression. J Biol Chem 281:13247–13257 (2006).
[PubMed]
100.
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).
[PubMed]
101.
Novak A, Guo C, Yang W, Nagy A, Lobe CG: Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision. Genesis 28:147–155 (2000).
[PubMed]
102.
Ottolenghi C, Omari S, Garcia-Ortiz JE, Uda M, Crisponi L, et al: Foxl2 is required for commitment to ovary differentiation. Hum Mol Genet 14:2053–2062 (2005).
[PubMed]
103.
Ottolenghi C, Uda M, Crisponi L, Omari S, Cao A, et al: Determination and stability of sex. BioEssays 29:15–25 (2007a).
[PubMed]
104.
Ottolenghi C, Pelosi E, Tran J, Colombino M, Douglass E, et al: Loss of Wnt4 and Foxl2 leads to female-to-male sex reversal extending to germ cells. Hum Mol Genet 16:2795–2804 (2007b).
[PubMed]
105.
Pailhoux E, Vigier B, Chaffaux S, Servel N, Taourit S, et al: A 11.7-kb deletion triggers intersexuality and polledness in goats. Nat Genet 29:453–458 (2001).
[PubMed]
106.
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).
[PubMed]
107.
Park JS, Valerius MT, McMahon AP: Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development. Development 134:2533–2539 (2007).
[PubMed]
108.
Parma P, Radi O, Vidal V, Chaboissier MC, Dellambra E, et al: R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet 38:1304–1309 (2006).
[PubMed]
109.
Patient RK, McGhee JD: The GATA family (vertebrates and invertebrates). Curr Opin Genet Dev 12:416–422 (2002).
[PubMed]
110.
Pepling ME, Spradling AC: Female mouse germ cells form synchronously dividing cysts. Development 125:3323–3328 (1998).
[PubMed]
111.
Richards JS, Pangas SA: The ovary: basic biology and clinical implications. J Clin Invest 120:963–972 (2010).
[PubMed]
112.
Schlessinger D, Garcia-Ortiz JE, Forabosco A, Uda M, Crisponi L, Pelosi E: Determination and stability of gonadal sex. J Androl 31:16–25 (2010).
[PubMed]
113.
Schmidt D, Ovitt CE, Anlag K, Fehsenfeld S, Gredsted L, et al: The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. Development 131:933–942 (2004).
[PubMed]
114.
Sekido R, Lovell-Badge R: Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature 453:930–934 (2008).
[PubMed]
115.
Semenov MV, Tamai K, Brott BK, Kuhl M, Sokol S, He X: Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol 11:951–961 (2001).
[PubMed]
116.
Shimizu H, Julius MA, Giarre M, Zheng Z, Brown AM, Kitajewski J: Transformation by WNT family proteins correlates with regulation of beta-catenin. Cell Growth Differ 8:1349–1358 (1997).
[PubMed]
117.
Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, et al: A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346:240–244 (1990).
[PubMed]
118.
Small CL, Shima JE, Uzumcu M, Skinner MK, Griswold MD: Profiling gene expression during the differentiation and development of the murine embryonic gonad. Biol Reprod 72:492–501 (2005).
[PubMed]
119.
Smith CA, Shoemaker CM, Roeszler KN, Queen J, Crews D, Sinclair AH: Cloning and expression of R-Spondin1 in different vertebrates suggests a conserved role in ovarian development. BMC Dev Biol 8:72 (2008).
[PubMed]
120.
Stark K, Vainio S, Vassileva G, McMahon AP: Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt4. Nature 372:679–683 (1994).
[PubMed]
121.
Swain A, Lovell-Badge R: Mammalian sex determination: a molecular drama. Genes Dev 13:755–767 (1999).
[PubMed]
122.
Taelman VF, Dobrowolski R, Plouhinec JL, Fuentealba LC, Vorwald PP, et al: Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell 143:1136–1148 (2010).
[PubMed]
123.
Tevosian SG, Manuylov NL: To β or not to β: canonical beta-catenin signaling pathway and ovarian development. Dev Dyn 237:3672–3680 (2008).
[PubMed]
124.
Tomaselli S, Megiorni F, De Bernardo C, Felici A, Marrocco G, et al: Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation. Hum Mutat 29:220–226 (2008).
[PubMed]
125.
Tomizuka K, Horikoshi K, Kitada R, Sugawara Y, Iba Y, et al: R-spondin1 plays an essential role in ovarian development through positively regulating Wnt4 signaling. Hum Mol Genet 17:1278–1291 (2008).
[PubMed]
126.
Townes PL, Muechler EK: Blepharophimosis, ptosis, epicanthus inversus, and primary amenorrhea. A dominant trait. Arch Ophthalmol 97:1664–1666 (1979).
[PubMed]
127.
Uda M, Ottolenghi C, Crisponi L, Garcia JE, Deiana M, et al: Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development. Hum Mol Genet 13:1171–1181 (2004).
[PubMed]
128.
Uhlenhaut NH, Treier M: Forkhead transcription factors in ovarian function. Reproduction (2011).
129.
Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, et al: Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell 139:1130–1142 (2009).
[PubMed]
130.
Vainio S, Heikkila M, Kispert A, Chin N, McMahon AP: Female development in mammals is regulated by Wnt4 signalling. Nature 397:405–409 (1999).
[PubMed]
131.
van Amerongen R, Nusse R: Towards an integrated view of Wnt signaling in development. Development 136:3205–3214 (2009).
[PubMed]
132.
Vernole P, Terrinoni A, Didona B, De Laurenzi V, Rossi P, et al: An SRY-negative XX male with Huriez syndrome. Clin Genet 57:61–66 (2000).
[PubMed]
133.
Vidal VP, Chaboissier MC, de Rooij DG, Schedl A: Sox9 induces testis development in XX transgenic mice. Nat Genet 28:216–217 (2001).
[PubMed]
134.
Viger RS, Guittot SM, Anttonen M, Wilson DB, Heikinheimo M: Role of the GATA family of transcription factors in endocrine development, function, and disease. Mol Endocrinol 22:781–798 (2008).
[PubMed]
135.
Vooijs M, Jonkers J, Berns A: A highly efficient ligand-regulated Cre recombinase mouse line shows that LoxP recombination is position dependent. EMBO Rep 2:292–297 (2001).
[PubMed]
136.
Wang D, Kobayashi T, Zhou L, Nagahama Y: Molecular cloning and gene expression of Foxl2 in the Nile tilapia, Oreochromis niloticus. Biochem Biophys Res Commun 320:83–89 (2004).
[PubMed]
137.
Washburn LL, Eicher EM: Sex reversal in XY mice caused by dominant mutation on chromosome 17. Nature 303:338–340 (1983).
[PubMed]
138.
Wei Q, Yokota C, Semenov MV, Doble B, Woodgett J, He X: R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and beta-catenin signaling. J Biol Chem 282:15903–15911 (2007).
[PubMed]
139.
Wilhelm D, Martinson F, Bradford S, Wilson MJ, Combes AN, et al: Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination. Dev Biol 287:111–124 (2005).
[PubMed]
140.
Wilhelm D, Palmer S, Koopman P: Sex determination and gonadal development in mammals. Physiol Rev 87:1–28 (2007).
[PubMed]
141.
Wilhelm D, Washburn LL, Truong V, Fellous M, Eicher EM, Koopman P: Antagonism of the testis- and ovary-determining pathways during ovotestis development in mice. Mech Dev 126:324–336 (2009).
[PubMed]
142.
Willert J, Epping M, Pollack JR, Brown PO, Nusse R: A transcriptional response to Wnt protein in human embryonic carcinoma cells. BMC Dev Biol 2:8 (2002).
[PubMed]
143.
Yao HH, DiNapoli L, Capel B: Meiotic germ cells antagonize mesonephric cell migration and testis cord formation in mouse gonads. Development 130:5895–5902 (2003).
[PubMed]
144.
Yao HH, Matzuk MM, Jorgez CJ, Menke DB, Page DC, et al: Follistatin operates downstream of Wnt4 in mammalian ovary organogenesis. Dev Dyn 230:210–215 (2004).
[PubMed]
145.
Yu HM, Jerchow B, Sheu TJ, Liu B, Costantini F, et al: The role of Axin2 in calvarial morphogenesis and craniosynostosis. Development 132:1995–2005 (2005).
[PubMed]
146.
Zaytouni T, Efimenko EE, Tevosian SG: GATA transcription factors in the developing reproductive system. Adv Genet 76:93–134 (2011).
[PubMed]
147.
Zhang H, Bradley A: Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122:2977–2986 (1996).
[PubMed]
© 2012 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2012
You do not currently have access to this content.
