A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary

English version České info

The formation of haploid gametes from diploid germ cells requires a specialized reductive cell division known as meiosis. This reductive division is enabled by chromosomal events that occur during meiotic prophase, including synapsis and crossing-over of homologous chromosomes. These chromosomal events involve meiosis-specific genes that must be expressed before they act during meiosis. Using gene expression profiling, we identified a set of mammalian meiosis-specific genes. To understand how expression of these genes is controlled, we examined their expression in the absence of known regulators of the chromosomal events: 1) retinoic acid (RA), which induces meiosis, 2) Dazl, which is required for germ cell competence to respond to RA, and 3) Stra8, which is induced by RA and is required for the chromosomal events of meiotic prophase. We uncover two key features of gene regulation. First, while the genes require RA and Dazl to be expressed, they vary in their dependence on Stra8, thus creating a regulatory hierarchy. Genes induced independently of Stra8, and thus early in this hierarchy, may encode proteins that are stockpiled in anticipation of the chromosomal events. Second, Stra8 induces its own down-regulation, and may thus prevent repeated induction of meiosis in a single germ cell.

Vyšlo v časopise: A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005531
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005531

Souhrn

Zdroje

1. Chu S, DeRisi J, Eisen M, Mulholland J, Botstein D, Brown PO, et al. The transcriptional program of sporulation in budding yeast. Science. 1998;282:699–705. doi: 10.1126/science.282.5389.699 9784122

2. Primig M, Williams RM, Winzeler EA, Tevzadze GG, Conway AR, Hwang SY, et al. The core meiotic transcriptome in budding yeasts. Nat Genet. 2000;26:415–423. doi: 10.1038/82539 11101837

3. Smith HE, Mitchell AP. A transcriptional cascade governs entry into meiosis in Saccharomyces cerevisiae. Mol Cell Biol. 1989;9:2142–2152. 2664470

4. Kassir Y, Adir N, Boger-Nadjar E, Raviv NG, Rubin-Bejerano I, Sagee S, et al. Transcriptional regulation of meiosis in budding yeast. Int Rev Cytol. 2003;224:111–71. Available: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2882377&tool=pmcentrez&rendertype=abstract 12722950

5. Handel MA, Schimenti JC. Genetics of mammalian meiosis: regulation, dynamics and impact on fertility. Nat Rev Genet. Nature Publishing Group; 2010;11:124–36. doi: 10.1038/nrg2723

6. Cohen PE, Pollack SE, Pollard JW. Genetic analysis of chromosome pairing, recombination, and cell cycle control during first meiotic prophase in mammals. Endocr Rev. 2006;27:398–426. doi: 10.1210/er.2005-0017 16543383

7. Marston AL, Amon A. Meiosis: cell-cycle controls shuffle and deal. Nat Rev Mol Cell Biol. 2004;5:983–97. doi: 10.1038/nrm1526 15573136

8. Schurko AM, Logsdon JM. Using a meiosis detection toolkit to investigate ancient asexual “scandals” and the evolution of sex. BioEssays. 2008;30:579–589. doi: 10.1002/bies.20764 18478537

9. Villeneuve AM, Hillers KJ. Whence meiosis? Cell. 2001;106:647–650. doi: 10.1016/S0092-8674(01)00500-1 11572770

10. Kumar R, Bourbon HM, De Massy B. Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice. Genes Dev. 2010;24:1266–1280. doi: 10.1101/gad.571710 20551173

11. Van Werven FJ, Amon A. Regulation of entry into gametogenesis. Philos Trans R Soc Lond B Biol Sci. 2011;366:3521–31. doi: 10.1098/rstb.2011.0081 22084379

12. Anderson EL, Baltus AE, Roepers-Gajadien HL, Hassold TJ, de Rooij DG, van Pelt AMM, 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;105:14976–14980. doi: 10.1073/pnas.0807297105 18799751

13. 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. doi: 10.1126/science.1125691 16574820

14. Koubova J, Menke DB, Zhou Q, Capel B, Griswold MD, Page DC. Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Natl Acad Sci. 2006;103:2474–2479. doi: 10.1073/pnas.0510813103 16461896

15. Fujiwara S, Kawamura K. Acquisition of retinoic acid signaling pathway and innovation of the chordate body plan. Zoolog Sci. Zoological Society of Japan; 2003;20:809–818. doi: 10.2108/zsj.20.809

16. Oulad-Abdelghani M, Bouillet P, Décimo D, Gansmuller A, Heyberger S, Dollé 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;135:469–477. doi: 10.1083/jcb.135.2.469 8896602

17. Zhou Q, Nie R, Li Y, Friel P, Mitchell D, Hess RA, et al. Expression of stimulated by retinoic acid gene 8 (Stra8) in spermatogenic cells induced by retinoic acid: an in vivo study in vitamin A-sufficient postnatal murine testes. Biol Reprod. 2008;79:35–42. doi: 10.1095/biolreprod.107.066795 18322276

18. Zhou Q, Li Y, Nie R, Friel P, Mitchell D, Evanoff RM, 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. doi: 10.1095/biolreprod.107.064337 18032419

19. Ghyselinck NB, Vernet N, Dennefeld C, Giese N, Nau H, Chambon P, et al. Retinoids and spermatogenesis: Lessons from mutant mice lacking the plasma retinol binding protein. Dev Dyn. 2006;235:1608–1622. doi: 10.1002/dvdy.20795 16586441

20. Baltus AE, Menke DB, Hu Y-C, Goodheart ML, Carpenter AE, de Rooij DG, et al. In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication. Nat Genet. 2006;38:1430–4. doi: 10.1038/ng1919 17115059

21. Lin Y, Gill ME, Koubova J, Page DC. Germ cell-intrinsic and -extrinsic factors govern meiotic initiation in mouse embryos. Science. 2008;322:1685–1687. doi: 10.1126/science.1166340 19074348

22. Gill ME, Hu Y-C, Lin Y, Page DC. Licensing of gametogenesis, dependent on RNA binding protein DAZL, as a gateway to sexual differentiation of fetal germ cells. Proc Natl Acad Sci. 2011;108:7443–8. doi: 10.1073/pnas.1104501108 21504946

23. Menke DB, Koubova J, Page DC. Sexual differentiation of germ cells in XX mouse gonads occurs in an anterior-to-posterior wave. Dev Biol. 2003;262:303–312. doi: 10.1016/S0012-1606(03)00391-9 14550793

24. Bullejos M, Koopman P. Germ cells enter meiosis in a rostro-caudal wave during development of the mouse ovary. Mol Reprod Dev. 2004;68:422–8. doi: 10.1002/mrd.20105 15236325

25. Speed RM. Meiosis in the foetal mouse ovary. I. An analysis at the light microscope level using surface-spreading. Chromosoma. 1982;85:427–37. Available: http://www.ncbi.nlm.nih.gov/pubmed/6180868 6180868

26. Borum K. Oogenesis in the mouse: a study of the meiotic prophase. Exp Cell Res. 1961;507:495–507. Available: http://www.sciencedirect.com/science/article/pii/0014482761904499

27. Handel MA, Eppig JJ. Sertoli cell differentiation in the testes of mice genetically deficient in germ cells. Biol Reprod. 1979;20:1031–1038. Available: http://www.biolreprod.org/content/20/5/1031.short 476239

28. McLaren A. Primordial germ cells in the mouse. Dev Biol. 2003;262:1–15. doi: 10.1016/S0012-1606(03)00214-8 14512014

29. Pesce M, Wang X, Wolgemuth DJ, Schöler H. Differential expression of the Oct-4 transcription factor during mouse germ cell differentiation. Mech Dev. 1998;71:89–98. Available: http://www.ncbi.nlm.nih.gov/pubmed/9507072 9507072

30. Yamaguchi S, Kimura H, Tada M, Nakatsuji N, Tada T. Nanog expression in mouse germ cell development. Gene Expr Patterns. 2005;5:639–646. doi: 10.1016/j.modgep.2005.03.001 15939376

31. Western P, Maldonado-Saldivia J, van den Bergen J, Hajkova P, Saitou M, Barton S, et al. Analysis of Esg1 expression in pluripotent cells and the germline reveals similarities with Oct4 and Sox2 and differences between human pluripotent cell lines. Stem Cells. 2005;23:1436–42. doi: 10.1634/stemcells.2005-0146 16166252

32. Koubova J, Hu Y-C, Bhattacharyya T, Soh YQS, Gill ME, Goodheart ML, et al. Retinoic acid activates two pathways required for meiosis in mice. PLoS Genet. 2014;10:e1004541. doi: 10.1371/journal.pgen.1004541 25102060

33. Raj A, van den Bogaard P, Rifkin S a, van Oudenaarden A, Tyagi S. Imaging individual mRNA molecules using multiple singly labeled probes. Nat Methods. 2008;5:877–879. doi: 10.1038/nmeth.1253 18806792

34. Lesch BJ, Dokshin GA, Young RA, McCarrey JR, Page DC. A set of genes critical to development is epigenetically poised in mouse germ cells from fetal stages through completion of meiosis. Proc Natl Acad Sci U S A. 2013;110:16061–6. doi: 10.1073/pnas.1315204110 24043772

35. Mahony S, Mazzoni EO, McCuine S, Young RA, Wichterle H, Gifford DK. Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis. Genome Biol. 2011;12:R2. doi: 10.1186/gb-2011-12-1-r2 21232103

36. Kalir S, Alon U. Using a quantitative blueprint to reprogram the dynamics of the flagella gene network. Cell. 2004;117:713–720. doi: 10.1016/j.cell.2004.05.010 15186773

37. Wang PJ, McCarrey JR, Yang F, Page DC. An abundance of X-linked genes expressed in spermatogonia. Nat Genet. 2001;27:422–6. doi: 10.1038/86927 11279525

38. Christophorou N, Rubin T, Huynh J-R. Synaptonemal complex components promote centromere pairing in pre-meiotic germ cells. PLoS Genet. 2013;9:e1004012. doi: 10.1371/journal.pgen.1004012 24367278

39. Joyce EF, Apostolopoulos N, Beliveau BJ, Wu C. Germline progenitors escape the widespread phenomenon of homolog pairing during Drosophila development. PLoS Genet. 2013;9:e1004013. doi: 10.1371/journal.pgen.1004013 24385920

40. Pasierbek P, Jantsch M, Melcher M, Schleiffer A, Schweizer D, Loidl J. A Caenorhabditis elegans cohesion protein with functions in meiotic chromosome pairing and disjunction. Genes Dev. 2001;15:1349–60. doi: 10.1101/gad.192701 11390355

41. Murdoch B, Owen N, Stevense M, Smith H, Nagaoka S, Hassold T, et al. Altered cohesin gene dosage affects mammalian meiotic chromosome structure and behavior. PLoS Genet. 2013;9:e1003241. doi: 10.1371/journal.pgen.1003241 23408896

42. Guttmann-Raviv N, Martin S, Kassir Y. Ime2, a meiosis-specific kinase in yeast, is required for destabilization of its transcriptional activator, Ime1. Mol Cell Biol. 2002;22:2047–2056. doi: 10.1128/MCB.22.7.2047-2056.2002 11884593

43. Foiani M, Nadjar-Boger E, Capone R, Sagee S, Hashimshoni T, Kassir Y. A meiosis-specific protein kinase, Ime2, is required for the correct timing of DNA replication and for spore formation in yeast meiosis. Mol Gen Genet. 1996;253:278–288. doi: 10.1007/s004380050323 9003314

44. Endo T, Romer K a., Anderson EL, Baltus AE, de Rooij DG, Page DC. Periodic retinoic acid—STRA8 signaling intersects with periodic germ-cell competencies to regulate spermatogenesis. Proc Natl Acad Sci. 2015;112:E2347–E2356. doi: 10.1073/pnas.1505683112 25902548

45. Oatley J, Hunt PA. Of mice and (wo)men: purified oogonial stem cells from mouse and human ovaries. Biol Reprod. 2012;86:196–196. doi: 10.1095/biolreprod.112.100297 22402962

46. Handel MA, Eppig JJ, Schimenti JC. Applying “gold standards” to in-vitro-derived germ cells. Cell. Elsevier; 2014;157:1257–1261. doi: 10.1016/j.cell.2014.05.019

47. Mintz B, Russell ES. Gene-induced embryological modifications of primordial germ cells in the mouse. J Exp Zool. 1957;134:207–37. Available: http://onlinelibrary.wiley.com/doi/10.1002/jez.1401340202/abstract 13428952

48. Waskow C, Paul S, Haller C, Gassmann M, Rodewald HR. Viable c-KitW/W mutants reveal pivotal role for c-Kit in the maintenance of lymphopoiesis. Immunity. 2002;17:277–288. doi: 10.1016/S1074-7613(02)00386-2 12354381

49. Tanosaki R, Migliaccio AR. Engraftment of normal stem cells in W/Wv mice assessed by a novel quantitative PCR analysis. Br J Haematol. 1997;98:1017–1025. doi: 10.1046/j.1365-2141.1997.2983115.x 9326206

50. Ruggiu M, Speed R, Taggart M, McKay SJ, Kilanowski F, Saunders P, et al. The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature. 1997;389:73–77. doi: 10.1038/37987 9288969

51. Trapnell C, Pachter L, Salzberg SL. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics. 2009;25:1105–11. doi: 10.1093/bioinformatics/btp120 19289445

52. Anders S, Pyl PT, Huber W. HTSeq—A Python framework to work with high-throughput sequencing data. Bioinformatics. 2014;31:166–169. doi: 10.1093/bioinformatics/btu638 25260700

53. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26:139–40. doi: 10.1093/bioinformatics/btp616 19910308

54. Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. Nature Publishing Group; 2010;28:511–5. doi: 10.1038/nbt.1621

55. De Hoon MJL, Imoto S, Nolan J, Miyano S. Open source clustering software. Bioinformatics. 2004;20:1453–4. doi: 10.1093/bioinformatics/bth078 14871861

56. Saldanha AJ. Java Treeview—extensible visualization of microarray data. Bioinformatics. 2004;20:3246–8. doi: 10.1093/bioinformatics/bth349 15180930

57. Peterson KA, Nishi Y, Ma W, Vedenko A, Shokri L, Zhang X, et al. Neural-specific Sox2 input and differential Gli-binding affinity provide context and positional information in Shh-directed neural patterning. Genes Dev. 2012;26:2802–2816. doi: 10.1101/gad.207142.112 23249739