Gene Symbol: Stra8
Description: stimulated by retinoic acid gene 8
Alias: stimulated by retinoic acid gene 8 protein
Species: mouse
Products:     Stra8

Top Publications

  1. Bogani D, Siggers P, Brixey R, Warr N, Beddow S, Edwards J, et al. Loss of mitogen-activated protein kinase kinase kinase 4 (MAP3K4) reveals a requirement for MAPK signalling in mouse sex determination. PLoS Biol. 2009;7:e1000196 pubmed publisher
  2. Menke D, Koubova J, Page D. Sexual differentiation of germ cells in XX mouse gonads occurs in an anterior-to-posterior wave. Dev Biol. 2003;262:303-12 pubmed
    ..Here, we traced the initiation of germ cell sexual differentiation in XX gonads using the Stra8 gene, which we demonstrate is an early molecular marker of female germ cell development...
  3. Bowles J, Koopman P. Retinoic acid, meiosis and germ cell fate in mammals. Development. 2007;134:3401-11 pubmed
    ..Although this knowledge clarifies a long-standing mystery in reproductive biology, it also poses many new questions, which we discuss in this review. ..
  4. Chassot A, Gregoire E, Lavery R, Taketo M, de Rooij D, Adams I, et al. RSPO1/?-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary. PLoS ONE. 2011;6:e25641 pubmed publisher
    ..In XX Rspo1(-/-) gonads, germ cell proliferation, expression of the early meiotic marker Stra8, and entry into meiosis are all impaired...
  5. Lin Y, Gill M, Koubova J, Page D. Germ cell-intrinsic and -extrinsic factors govern meiotic initiation in mouse embryos. Science. 2008;322:1685-7 pubmed publisher
    ..Within a brief developmental window, Dazl-expressing germ cells in both XX and XY embryos actively acquire the ability to interpret RA as a meiosis-inducing signal. ..
  6. Best D, Sahlender D, Walther N, Peden A, Adams I. Sdmg1 is a conserved transmembrane protein associated with germ cell sex determination and germline-soma interactions in mice. Development. 2008;135:1415-25 pubmed publisher
    ..These data suggest that changes that occur in the cell biology of embryonic Sertoli cells may facilitate the communication of male sex-determining decisions to the germ cells during embryonic development. ..
  7. Krentz A, Murphy M, Sarver A, Griswold M, Bardwell V, Zarkower D. DMRT1 promotes oogenesis by transcriptional activation of Stra8 in the mammalian fetal ovary. Dev Biol. 2011;356:63-70 pubmed publisher testicular differentiation is well established, and includes transcriptional repression of the meiotic inducer Stra8. However Dmrt1 mutant females are fertile and the role of Dmrt1 in the ovary has not been studied...
  8. Saba R, Wu Q, Saga Y. CYP26B1 promotes male germ cell differentiation by suppressing STRA8-dependent meiotic and STRA8-independent mitotic pathways. Dev Biol. 2014;389:173-81 pubmed publisher
    ..CYP26B1-null XY gonads, germ cells are exposed to a higher level of RA than in normal XY gonads and this activates Stra8 to induce meiosis while male-specific gene expression is suppressed...
  9. Suzuki A, Saba R, Miyoshi K, Morita Y, Saga Y. Interaction between NANOS2 and the CCR4-NOT deadenylation complex is essential for male germ cell development in mouse. PLoS ONE. 2012;7:e33558 pubmed publisher

More Information


  1. Li H, MacLean G, Cameron D, Clagett Dame M, Petkovich M. Cyp26b1 expression in murine Sertoli cells is required to maintain male germ cells in an undifferentiated state during embryogenesis. PLoS ONE. 2009;4:e7501 pubmed publisher
  2. Lavery R, Lardenois A, Ranc Jianmotamedi F, Pauper E, Gregoire E, Vigier C, et al. XY Sox9 embryonic loss-of-function mouse mutants show complete sex reversal and produce partially fertile XY oocytes. Dev Biol. 2011;354:111-22 pubmed publisher
    ..Taken together, we found that XY Sf1:Cre(Tg/+); Sox9(flox/flox) females are capable of producing viable offspring albeit at a reduced level. ..
  3. Warr N, Bogani D, Siggers P, Brixey R, Tateossian H, Dopplapudi A, et al. Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1. PLoS ONE. 2011;6:e19572 pubmed publisher
    ..Based on these observations, we conclude that MAP3K1 is not required for mouse testis determination. We discuss the significance of these data for the functional interpretation of sex-reversing MAP3K1 mutations in humans. ..
  4. Anderson E, Baltus A, Roepers Gajadien H, Hassold T, de Rooij D, van Pelt A, et al. Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice. Proc Natl Acad Sci U S A. 2008;105:14976-80 pubmed publisher
    ..b>Stra8 is a vertebrate-specific, cytoplasmic factor expressed by germ cells in response to retinoic acid...
  5. Chassot A, Ranc F, Gregoire E, Roepers Gajadien H, Taketo M, Camerino G, et al. Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet. 2008;17:1264-77 pubmed publisher
    ..Thus, a balance between Sox9 and beta-catenin activation determines the fate of the gonad, with Rspo1 acting as a crucial regulator of canonical beta-catenin signaling required for female development. ..
  6. Bowles J, Feng C, Spiller C, Davidson T, Jackson A, Koopman P. FGF9 suppresses meiosis and promotes male germ cell fate in mice. Dev Cell. 2010;19:440-9 pubmed publisher
  7. Bagheri Fam S, Sim H, Bernard P, Jayakody I, Taketo M, Scherer G, et al. Loss of Fgfr2 leads to partial XY sex reversal. Dev Biol. 2008;314:71-83 pubmed
    ..In summary, we provide evidence that FGFR2 is important for male sex determination in mice, thereby rendering human FGFR2 a candidate gene for unsolved DSD cases such as 10q26 deletions. ..
  8. Bowles J, Knight D, Smith C, Wilhelm D, Richman J, Mamiya S, et al. Retinoid signaling determines germ cell fate in mice. Science. 2006;312:596-600 pubmed
    ..Thus, precise regulation of retinoid levels during fetal gonad development provides the molecular control mechanism that specifies germ cell fate. ..
  9. Baltus A, Menke D, Hu Y, Goodheart M, Carpenter A, de Rooij D, et al. In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication. Nat Genet. 2006;38:1430-4 pubmed
    ..The mouse Stra8 gene is expressed in germ cells of embryonic ovaries, where meiosis is initiated, but not in those of embryonic ..
  10. Koubova J, Menke D, Zhou Q, Capel B, Griswold M, Page D. Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Natl Acad Sci U S A. 2006;103:2474-9 pubmed
    ..In mice, the Stimulated by Retinoic Acid Gene 8 (Stra8) has been found to be required for the transition into meiosis in both female and male germ cells...
  11. Gregoire E, Lavery R, Chassot A, Akiyama H, Treier M, Behringer R, et al. Transient development of ovotestes in XX Sox9 transgenic mice. Dev Biol. 2011;349:65-77 pubmed publisher
    ..Finally, ovarian cells of the XX Wt1:Sox9 ovotestis undergo apoptosis during late embryogenesis leading to complete female-to-male sex reversal of the transgenic mice at birth...
  12. Oulad Abdelghani M, Bouillet P, Decimo D, Gansmuller A, Heyberger S, Dolle P, et al. Characterization of a premeiotic germ cell-specific cytoplasmic protein encoded by Stra8, a novel retinoic acid-responsive gene. J Cell Biol. 1996;135:469-77 pubmed
    The full-length cDNA corresponding to Stra8, a novel gene inducible by retinoic acid (RA) in P19 embryonal carcinoma cells, has been isolated and shown to encode a 45-kD protein...
  13. Warr N, Carré G, Siggers P, Faleato J, Brixey R, Pope M, et al. Gadd45? and Map3k4 interactions regulate mouse testis determination via p38 MAPK-mediated control of Sry expression. Dev Cell. 2012;23:1020-31 pubmed publisher
    ..Taken together, our data suggest a requirement for GADD45? in promoting MAP3K4-mediated activation of p38 MAPK signaling in embryonic gonadal somatic cells for testis determination in the mouse. ..
  14. Kumar R, Ghyselinck N, Ishiguro K, Watanabe Y, Kouznetsova A, Höög C, et al. MEI4 – a central player in the regulation of meiotic DNA double-strand break formation in the mouse. J Cell Sci. 2015;128:1800-11 pubmed publisher
  15. Lee H, Pazin D, Kahlon R, Correa S, Albrecht K. Novel markers of early ovarian pre-granulosa cells are expressed in an Sry-like pattern. Dev Dyn. 2009;238:812-25 pubmed publisher
  16. Saba R, Kato Y, Saga Y. NANOS2 promotes male germ cell development independent of meiosis suppression. Dev Biol. 2014;385:32-40 pubmed publisher
    ..In this study, we addressed the issue by generating Nanos2/Stra8 double knockout (dKO) mice, whereby meiosis was prohibited in the double-mutant male germ cells...
  17. Geyer C, Saba R, Kato Y, Anderson A, Chappell V, Saga Y, et al. Rhox13 is translated in premeiotic germ cells in male and female mice and is regulated by NANOS2 in the male. Biol Reprod. 2012;86:127 pubmed publisher
    ..These results strongly suggest that RHOX13 expression is regulated at a posttranscriptional step by direct interaction of NANOS2 with Rhox13 mRNA to suppress translation. ..
  18. Kato Y, Katsuki T, Kokubo H, Masuda A, Saga Y. Dazl is a target RNA suppressed by mammalian NANOS2 in sexually differentiating male germ cells. Nat Commun. 2016;7:11272 pubmed publisher
    ..We propose a dual system of NANOS2-mediated suppression of Dazl expression as a pivotal molecular mechanism promoting sexual differentiation of XY germ cells. ..
  19. Busada J, Chappell V, Niedenberger B, Kaye E, Keiper B, Hogarth C, et al. Retinoic acid regulates Kit translation during spermatogonial differentiation in the mouse. Dev Biol. 2015;397:140-9 pubmed publisher
    ..Our findings provide an important molecular link between a morphogen (RA) and the expression of KIT protein, which together direct the differentiation of spermatogonia throughout the male reproductive lifespan. ..
  20. Soh Y, Junker J, Gill M, Mueller J, van Oudenaarden A, Page D. A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary. PLoS Genet. 2015;11:e1005531 pubmed publisher
    ..acid (RA), which induces meiosis, 2) Dazl, which is required for germ cell competence to respond to RA, and 3) Stra8, a downstream target of RA required for the chromosomal program of meiotic prophase...
  21. Kumar S, Chatzi C, Brade T, Cunningham T, Zhao X, Duester G. Sex-specific timing of meiotic initiation is regulated by Cyp26b1 independent of retinoic acid signalling. Nat Commun. 2011;2:151 pubmed
    ..initiation of meiosis in the fetal ovary has been suggested to require retinoic acid (RA) for induction of Stra8, with expression of the RA-degrading enzyme Cyp26b1 in fetal testis delaying meiosis until postnatal development...
  22. Pirouz M, Pilarski S, Kessel M. A critical function of Mad2l2 in primordial germ cell development of mice. PLoS Genet. 2013;9:e1003712 pubmed publisher
    ..Together, these results demonstrate the potential of Mad2l2 in the regulation of both cell cycle and the epigenetic status. The function of Mad2l2 is essential in PGCs, and thus of high relevance for fertility. ..
  23. Raverot G, Weiss J, Park S, Hurley L, Jameson J. Sox3 expression in undifferentiated spermatogonia is required for the progression of spermatogenesis. Dev Biol. 2005;283:215-25 pubmed
    ..We conclude that Sox3 is expressed in A(s), A(pr) and A(al) spermatogonia and is required for spermatogenesis through a pathway that involves Ngn3. ..
  24. Abby E, Tourpin S, Ribeiro J, Daniel K, Messiaen S, Moison D, et al. Implementation of meiosis prophase I programme requires a conserved retinoid-independent stabilizer of meiotic transcripts. Nat Commun. 2016;7:10324 pubmed publisher
    ..Remarkably, the upregulation of MEIOC at the onset of meiosis does not require retinoic acid and STRA8 signalling...
  25. Yokobayashi S, Liang C, Kohler H, Nestorov P, Liu Z, Vidal M, et al. PRC1 coordinates timing of sexual differentiation of female primordial germ cells. Nature. 2013;495:236-40 pubmed publisher
    ..In mouse female PGCs, expression of stimulated by retinoic acid gene 8 (Stra8) and meiosis are induced in response to retinoic acid provided from the mesonephroi...
  26. Lavery R, Chassot A, Pauper E, Gregoire E, Klopfenstein M, de Rooij D, et al. Testicular differentiation occurs in absence of R-spondin1 and Sox9 in mouse sex reversals. PLoS Genet. 2012;8:e1003170 pubmed publisher
    ..The dogma that considers female differentiation as a default pathway therefore needs to be definitively revised. ..
  27. Zheng Y, Tan X, Pyczek J, Nolte J, Pantakani D, Engel W. Generation and characterization of yeast two-hybrid cDNA libraries derived from two distinct mouse pluripotent cell types. Mol Biotechnol. 2013;54:228-37 pubmed publisher
    ..Finally, we would like to make these cDNA libraries as a resource that can be distributed to the research community. ..
  28. Garcia T, Farmaha J, Kow S, Hofmann M. RBPJ in mouse Sertoli cells is required for proper regulation of the testis stem cell niche. Development. 2014;141:4468-78 pubmed publisher
  29. Heaney J, Anderson E, Michelson M, Zechel J, Conrad P, Page D, et al. Germ cell pluripotency, premature differentiation and susceptibility to testicular teratomas in mice. Development. 2012;139:1577-86 pubmed publisher
    ..embryonic female and adult male germ cells, including cyclin D1 (Ccnd1) and stimulated by retinoic acid 8 (Stra8), were prematurely expressed in teratoma-susceptible germ cells and, in rare instances, induced entry into meiosis...
  30. Pui H, Saga Y. Gonocytes-to-spermatogonia transition initiates prior to birth in murine testes and it requires FGF signaling. Mech Dev. 2017;144:125-139 pubmed publisher
    ..Taken together, we defined the precise timing of GST and revealed FGF signaling as a master regulator of GST in the perinatal mouse testes. ..
  31. Zhou Q, Li Y, Nie R, Friel P, Mitchell D, Evanoff R, et al. Expression of stimulated by retinoic acid gene 8 (Stra8) and maturation of murine gonocytes and spermatogonia induced by retinoic acid in vitro. Biol Reprod. 2008;78:537-45 pubmed
    ..The expression of Stimulated by retinoic acid gene 8 (Stra8), which is required for spermatogenesis, is directly related to the availability of retinoic acid (RA)...
  32. Suzuki A, Niimi Y, Saga Y. Interaction of NANOS2 and NANOS3 with different components of the CNOT complex may contribute to the functional differences in mouse male germ cells. Biol Open. 2014;3:1207-16 pubmed publisher
    ..This alternate interaction might account for the molecular basis of the functional redundancy and differences in NANOS2 and NANOS3 functions. ..
  33. Shum E, Jones S, Shao A, Dumdie J, Krause M, Chan W, et al. The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay. Cell. 2016;165:382-95 pubmed publisher
    ..Mice conditionally lacking UPF3A exhibit "hyper" NMD and display defects in embryogenesis and gametogenesis. Our results support a model in which UPF3A serves as a molecular rheostat that directs developmental events. ..
  34. Desimio M, Campolo F, Dolci S, De Felici M, Farini D. SOHLH1 and SOHLH2 directly down-regulate STIMULATED BY RETINOIC ACID 8 (STRA8) expression. Cell Cycle. 2015;14:1036-45 pubmed publisher
    ..we demonstrate a direct negative control of SOHLH1 and SOHLH2, 2 germ cell specific bHLH transcription factors, on Stra8 expression...
  35. Vanhoutteghem A, Messiaen S, Hervé F, Delhomme B, Moison D, Petit J, et al. The zinc-finger protein basonuclin 2 is required for proper mitotic arrest, prevention of premature meiotic initiation and meiotic progression in mouse male germ cells. Development. 2014;141:4298-310 pubmed publisher
    ..methylation protein DNMT3L and have increased levels of mRNAs that encode meiotic proteins, including STRA8. Bnc2(-/-) prospermatogonia can produce spermatogonia, but these enter meiosis prematurely and undergo massive ..
  36. Siggers P, Carré G, Bogani D, Warr N, Wells S, Hilton H, et al. A novel mouse Fgfr2 mutant, hobbyhorse (hob), exhibits complete XY gonadal sex reversal. PLoS ONE. 2014;9:e100447 pubmed publisher
    ..We exploited the consistent phenotype of this constitutive mutant by analysing MAPK signalling at the sex-determining stage of gonad development, but no significant abnormalities in mutant embryos were detected. ..
  37. Small C, Shima J, Uzumcu M, Skinner M, Griswold M. Profiling gene expression during the differentiation and development of the murine embryonic gonad. Biol Reprod. 2005;72:492-501 pubmed
  38. Miles D, Van Den Bergen J, Wakeling S, Anderson R, Sinclair A, Western P. The proto-oncogene Ret is required for male foetal germ cell survival. Dev Biol. 2012;365:101-9 pubmed publisher
    ..Either way, this study identifies the proto-oncogene RET as a novel component of the foetal male germ cell development pathway. ..
  39. Zhou Z, Shirakawa T, Ohbo K, Sada A, Wu Q, Hasegawa K, et al. RNA Binding Protein Nanos2 Organizes Post-transcriptional Buffering System to Retain Primitive State of Mouse Spermatogonial Stem Cells. Dev Cell. 2015;34:96-107 pubmed publisher
    ..This mechanism links mRNA turnover to mTORC1 signaling through Nanos2-containing mRNPs and establishes a post-transcriptional buffering system to facilitate SSC homeostasis in the fluctuating environment within the seminiferous tubule. ..
  40. Piprek R, Kolasa M, Podkowa D, Kloc M, Kubiak J. Cell adhesion molecules expression pattern indicates that somatic cells arbitrate gonadal sex of differentiating bipotential fetal mouse gonad. Mech Dev. 2017;147:17-27 pubmed publisher
    ..This indicates that differential CAMs expression pattern in the somatic cells but not in the germ line arbitrates structural organization of gonadal anlagen into testis or ovary. ..
  41. Liu K, Sun X, Feng Y, Cheng S, Li B, Li Y, et al. The impact of Zearalenone on the meiotic progression and primordial follicle assembly during early oogenesis. Toxicol Appl Pharmacol. 2017;329:9-17 pubmed publisher
    ..In conclusion, ZEA exposure impairs mouse female germ cell meiotic progression, DNA-DSBs, and primordial follicle assembly. ..
  42. Shin Y, Ren Y, Suzuki H, Golnoski K, Ahn H, Mico V, et al. Transcription factors SOHLH1 and SOHLH2 coordinate oocyte differentiation without affecting meiosis I. J Clin Invest. 2017;127:2106-2117 pubmed publisher
    ..Our results indicate that Sohlh1 and Sohlh2 are essential regulators of oocyte differentiation but do not affect meiosis I. ..
  43. Dokshin G, Baltus A, Eppig J, Page D. Oocyte differentiation is genetically dissociable from meiosis in mice. Nat Genet. 2013;45:877-83 pubmed publisher
    Oogenesis is the process by which ovarian germ cells undertake meiosis and differentiate to become eggs. In mice, Stra8 is required for the chromosomal events of meiosis to occur, but its role in differentiation remains unknown...
  44. Chihara M, Ikebuchi R, Otsuka S, Ichii O, Hashimoto Y, Suzuki A, et al. Mice stage-specific claudin 3 expression regulates progression of meiosis in early stage spermatocytes. Biol Reprod. 2013;89:3 pubmed publisher
    ..Furthermore, claudin 3 protein was localized not only to the BTB but also to the cell membrane of STRA8-expressing preleptotene/leptotene spermatocytes in the testis of adult ICR.Cg-Tg(Stra8-EGFP)1Ysa/YsaRbrc mice...
  45. Krentz A, Murphy M, Zhang T, Sarver A, Jain S, Griswold M, et al. Interaction between DMRT1 function and genetic background modulates signaling and pluripotency to control tumor susceptibility in the fetal germ line. Dev Biol. 2013;377:67-78 pubmed publisher
    ..Given the strong evidence for involvement of DMRT1 in human TGCT, the downstream genes and pathways identified in this study provide potentially useful candidates for roles in the human disease. ..
  46. Antonangeli F, Giampietri C, Petrungaro S, Filippini A, Ziparo E. Expression profile of a 400-bp Stra8 promoter region during spermatogenesis. Microsc Res Tech. 2009;72:816-22 pubmed publisher
    ..A 400-bp regulatory region of the stimulated by retinoic acid gene 8 (Stra8) promoter was reported to direct gene expression into SSCs and we have recently generated a new transgenic mouse ..
  47. Koubova J, Hu Y, Bhattacharyya T, Soh Y, Gill M, Goodheart M, et al. Retinoic acid activates two pathways required for meiosis in mice. PLoS Genet. 2014;10:e1004541 pubmed publisher
    ..In mice, retinoic acid (RA), the extrinsic signal for meiotic initiation, activates transcription of Stra8, which is required for meiotic DNA replication and the subsequent processes of meiotic prophase...
  48. Ohta K, Yamamoto M, Lin Y, Hogg N, Akiyama H, Behringer R, et al. Male differentiation of germ cells induced by embryonic age-specific Sertoli cells in mice. Biol Reprod. 2012;86:112 pubmed publisher
    ..5 and 12.5 days postcoitus (dpc) with an RA receptor inhibitor. Expression of Stra8, a meiosis initiation gene, was suppressed in all groups...
  49. Umehara T, Kawashima I, Kawai T, Hoshino Y, Morohashi K, Shima Y, et al. Neuregulin 1 Regulates Proliferation of Leydig Cells to Support Spermatogenesis and Sexual Behavior in Adult Mice. Endocrinology. 2016;157:4899-4913 pubmed
  50. Le Bouffant R, Souquet B, Duval N, Duquenne C, Hervé R, Frydman N, et al. Msx1 and Msx2 promote meiosis initiation. Development. 2011;138:5393-402 pubmed publisher
    ..In vivo, the Msx1/Msx2 double-null mutation prevented full activation of Stra8, a gene required for meiosis...
  51. Mark M, Jacobs H, Oulad Abdelghani M, Dennefeld C, Féret B, Vernet N, et al. STRA8-deficient spermatocytes initiate, but fail to complete, meiosis and undergo premature chromosome condensation. J Cell Sci. 2008;121:3233-42 pubmed publisher
    We analysed the phenotypic outcome of a Stra8-null mutation on male meiosis...
  52. Miyamoto T, Sengoku K, Takuma N, Hasuike S, Hayashi H, Yamauchi T, et al. Isolation and expression analysis of the testis-specific gene, STRA8, stimulated by retinoic acid gene 8. J Assist Reprod Genet. 2002;19:531-5 pubmed
    ..The Stra8 gene encodes a cytoplasmic protein and is expressed specific to the developing male gonad during mouse ..
  53. Warr N, Siggers P, Carré G, Wells S, Greenfield A. Genetic Analyses Reveal Functions for MAP2K3 and MAP2K6 in Mouse Testis Determination. Biol Reprod. 2016;94:103 pubmed publisher
    ..25 days postcoitum. Our data suggest that MAP2K6 functions in mouse testis determination, via positive effects on Sry, and also indicate a minor role for MAP2K3. ..