A very recent study suggests that XY germ cells remain meiosis-competent up to at least Apparent discrepancies with respect to the end of the period of meiotic competence are likely to reflect the fact that germ cells do not tend to act in concert and processes such as meiosis entry and mitotic arrest occur over several days. Hence, a sub-population of XY germ cells may be refractory to meiosis induction by Intrinsic factors that underlie meiotic competence are yet to be defined, but some candidates have emerged in recent years.
Germ cells normally upregulate Ddx4 only after reaching the gonads, and it is not known what triggers this change in expression Tanaka et al. DDX4 continues to be expressed throughout embryogenesis in germ cells of the fetal testis and ovary and in spermatocytes, postmeiotic spermatids, and primary oocytes postnatally Fujiwara et al. These results suggest that Ddx4 expression is induced when germ cells come into contact with gonadal somatic cells, and that ESCs are less competent to respond than EGCs.
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Interestingly, germ cells in the adrenal not only enter meiosis but also express Ddx4 Runyan et al. It may be that those germ cells are encountering competence-inducing signals that are the same or similar to signals produced by fetal gonadal cells.
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It is not likely, however, that expression of Ddx4 alone ensures competence to enter meiosis since ablation of Ddx4 does not affect normal oogenesis. In the male, DDX4 is not required for entry into meiosis but is required for the continued proliferation and differentiation of germ cells in the testis Tanaka et al. Since this marker is also observed when 8. It is also possible, however, that the necessary inducing signals are present in cell culture media and in the adrenal and peri-gonadal environments.
Interestingly, both pre-migratory 8. Possibly GCNA1 expression upon entry into the gonad is related to the significant changes in demethylation and chromatin structure that occur at that time. Nonetheless, DAZL is extremely important for the continued development of germ cells once they colonize the gonad.
Expression of Dazl seems to be necessary for correct methylation erasure of at least the H19 imprinted locus and for normal levels of expression of Ddx4 upon entry into the gonad Reynolds et al. It is possible that DAZL works to affect translation of a number of germ line- and meiosis-specific transcripts. A recent report demonstrates that, when Dazl is overexpressed in mESCs, germ cells can be derived directly, without the need for embryoid body formation Yu et al. Sex determination of the germ cell lineage, in the mammal, occurs in the gonad during fetal development.
Germ cells either enter meiosis, and thereby commit to the oogenic pathway, or avoid entry into meiosis, enter a state of quiescence and commit to the spermatogenic pathway. A thorough understanding of germ cell sex determination is important because aberrations in the process underlie infertility and the development of germ cell tumors.
Knowledge of the intricacies of the in vivo mechanisms may also aid future attempts to generate gametes in vitro Feng et al. The specification of PGCs from a field of pluripotent epiblast cells is dependent on BMP and WNT3 signaling molecules, which seem to induce competence to become the germ cell lineage Surani et al. In addition, germ cells at various stages of the process are characterized by particular epigenetic signatures and chromatin architectures.
The migration, proliferation, and survival of germ cells as they journey through the embryo seem to be dependent on a number of extrinsic factors. The nature of germ cell development is such that that the cells are at different times in different somatic environments — this may ensure the characteristic genetic and epigenetic states observed at various times.
By the time the germ cells enter the gonad they appear to have matured to the point where they are able to respond to an extrinsic cue to enter meiosis Fig. The extrinsic cue is now firmly established as RA Baltus et al. XY and XX germ cells are competent to be pushed into meiotic prophase even earlier than XX germ cells do in vivo Bowles et al. Presumably XY germ cells remain meiosis-competent until they commit to the male programme at around Figure 3 Download Figure Download figure as PowerPoint slide Key intrinsic and extrinsic factors involved in sex determination in murine fetal germ cells.
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In the presence of RA, produced by somatic cells, germ cells begin to express Stra8 at about Ultimately, meiotic marker genes are upregulated, and the germ cells enter prophase I of meiosis thereby committing to the female fate. Mitotic arrest, possibly due to the absence of RA, begins in some germ cells as early as A secreted testis-specific factor or factors, as yet unidentified, are likely to signal to the germ cells.
By These spermatogonia express markers of male fate such as Dnmt3l and Tdrd1. Timing of various processes is approximate. Commitment to the male programme, as delineated by both mitotic arrest and the expression of male germ cell fate markers such as Nanos2 and Dnmt3l , is likely to be prompted by a male-specific gonadal signaling factor or factors , as yet unidentified Fig. Mitotic arrest in the developing testis appears to occur only in the absence of RA Trautmann et al. Although we are making progress in understanding mammalian germ cell sex determination, a great deal remains mysterious.
It is not clear to what extent germ cells are pre-programmed to develop and differentiate and to what extent their intrinsic nature at each step reflects the extrinsic signals they have been exposed to. Future studies will focus on key genes Stra8 , Dazl , and Nanos2 and on the identity of postulated extrinsic signaling molecules that are relevant to the process. RNA-binding proteins are likely to important, as they are in other species during the sex determination phase of germ cell development.
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this work. We thank Antoine Rolland and Cassy Spiller for their critical reading of the manuscript, and anonymous referees for their helpful comments. Adams IR McLaren A Sexually dimorphic development of mouse primordial germ cells: switching from oogenesis to spermatogenesis.
Development — Genetics — Nature Cell Biology 8 — PNAS — Genes and Development 22 — Nature Genetics 38 — Mechanisms of Development 91 — Human Reproduction 21 30 — BMC Developmental Biology 4 2. Developmental Biology — Nature 96 — Science — Bowles J Koopman P Retinoic acid, meiosis and germ cell fate in mammals.
Bullejos M Koopman P Germ cells enter meiosis in a rostro-caudal wave during development of the mouse ovary. Molecular Reproduction and Development 68 — Byskov AG Does the rete ovarii act as a trigger for the onset of meiosis? Nature — Byskov AG The role of the rete ovarii in meiosis and follicle formation in the cat, mink and ferret. Journal of Reproduction and Fertility 45 — Developmental Biology 52 — Chuma S Nakatsuji N Autonomous transition into meiosis of mouse fetal germ cells in vitro and its inhibition by gpmediated signaling.
Mechanisms of Development — Sexual Development 2 — Endocrinology — International Journal of Developmental Biology 44 — BMC Developmental Biology 8 A systematic study of their differential pattern of transcription during mouse organogenesis. Cell 44 — Mechanisms of Development 68 — Duester G Retinoic acid synthesis and signaling during early organogenesis. Cell — Enders GC May JJ II Developmentally regulated expression of a mouse germ cell nuclear antigen examined from embryonic day 11 to adult in male and female mice. Developmental Biology 49 — Francavilla S Zamboni L Differentiation of mouse ectopic germinal cells in intra- and perigonadal locations.
Journal of Experimental Zoology — Fuchs E Green H Regulation of terminal differentiation of cultured human keratinocytes by vitamin A. Cell 25 — PNAS 91 — Mechanisms of Development 15 — Developmental Dynamics — Haston KM Tung JY Reijo Pera RA Dazl functions in maintenance of pluripotency and genetic and epigenetic programs of differentiation in mouse primordial germ cells in vivo and in vitro. Comparative histological and autoradiographic studies of oocytes and transitional prospermatogonia during oogenesis and prespermatogenesis. Cell and Tissue Research — Human Molecular Genetics 16 — Koshimizu U Watanabe M Nakatsuji N Retinoic acid is a potent growth activator of mouse primordial germ cells in vitro.
Molecular and Cellular Biology 28 — Ciba Foundation Symposia 68 — 84 discussion 84— Genes and Development 13 — Li H Clagett-Dame M Vitamin A deficiency blocks the initiation of meiosis of germ cells in the developing rat ovary in vivo. Biology of Reproduction 81 — MacGregor GR Zambrowicz BP Soriano P Tissue non-specific alkaline phosphatase is expressed in both embryonic and extraembryonic lineages during mouse embryogenesis but is not required for migration of primordial germ cells. Biology of Reproduction 73 — Journal of Cell Science — Nuclear Receptor Signaling 7 e McLaren A Sex chimaerism and germ cell distribution in a series of chimaeric mice.
Journal of Embryology and Experimental Morphology 33 — McLaren A The fate of germ cells in the testis of fetal sex-reversed mice. Journal of Reproduction and Fertility 61 — McLaren A Meiosis and differentiation of mouse germ cells. Symposia of the Society for Experimental Biology 38 7 — McLaren A Primordial germ cells in the mouse. Developmental Biology 1 — Gene Expression Patterns 2 — Molyneaux KA Wang Y Schaible K Wylie C Transcriptional profiling identifies genes differentially expressed during and after migration in murine primordial germ cells.
Gene Expression Patterns 4 — Journal of Embryology and Experimental Morphology 63 75 — Monk M Boubelik M Lehnert S Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development 99 — Morita Y Tilly JL Segregation of retinoic acid effects on fetal ovarian germ cell mitosis versus apoptosis by requirement for new macromolecular synthesis.
Developmental Cell 11 — Niwa H Open conformation chromatin and pluripotency. Genes and Development 21 — Journal of Reproduction and Fertility 48 — Ohkubo Y Shirayoshi Y Nakatsuji N Autonomous regulation of proliferation and growth arrest in mouse primordial germ cells studied by mixed and clonal cultures.
Experimental Cell Research — Journal of Cell Biology — Journal of Cellular Physiology 87 — Human Molecular Genetics 14 — RNA 13 — Biology of Reproduction 61 — Richardson BE Lehmann R Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nature Reviews. Molecular Cell Biology 11 37 — Genes and Development 5 — Nature 73 — International Journal of Developmental Biology 52 — Saitou M a Germ cell specification in mice.
Saitou M b Specification of the germ cell lineage in mice. Frontiers in Bioscience 14 — Cell Cycle 4 — Gene Expression Patterns 5 — Molecular Reproduction and Development 65 41 — Reproduction — Seligman J Page DC The Dazh gene is expressed in male and female embryonic gonads before germ cell sex differentiation.
Biochemical and Biophysical Research Communications — Vitamins and Hormones 75 69 — Genes and Development 18 — Speed RM Meiosis in the foetal mouse ovary. An analysis at the light microscope level using surface-spreading. Chromosoma 85 — Biology of Reproduction 82 — Journal of the National Cancer Institute 50 — Sugimoto M Abe E X chromosome reactivation initiates in nascent primordial germ cells in mice. PLoS Genetics 3 e Suzuki A Saga Y Nanos2 suppresses meiosis and promotes male germ cell differentiation.
Szabo PE Mann JR Biallelic expression of imprinted genes in the mouse germ line: implications for erasure, establishment, and mechanisms of genomic imprinting. Genes and Development 9 — Development Genes and Evolution — Tam PP Zhou SX The allocation of epiblast cells to ectodermal and germ-line lineages is influenced by the position of the cells in the gastrulating mouse embryo. Genes and Development 14 — Developmental Cell 9 — Journal of Biological Chemistry — Developmental Cell 6 — Mechanisms of Development 93 — Cell Cycle 7 — Upadhyay S Zamboni L Ectopic germ cells: natural model for the study of germ cell sexual differentiation.
PNAS 79 — Development 43 — Wang N Tilly JL Epigenetic status determines germ cell meiotic commitment in embryonic and postnatal mammalian gonads.
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Cell Cycle 9 — Molecular Reproduction and Development 48 — Current Biology 13 — Stem Cells 26 — Wylie C Germ cells. Cell 96 — Biology of Reproduction 75 — Nature Genetics 40 — Molecular Endocrinology 14 — Journal of Molecular Cell Biology 1 93 — Zamboni L Upadhyay S Germ cell differentiation in mouse adrenal glands. Specification of mouse PGCs. Intrinsic changes observed in germ cells upon colonization of the gonad.
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Key intrinsic and extrinsic factors involved in sex determination in murine fetal germ cells. Introduction Germ cells are the special cells of the embryo that ultimately give rise to the spermatozoa and oocytes. Making, moving, and maturing the germ cells In the mouse embryo, germ cells are specified from about 6. Specification and transcriptional identity of the germ line In many species, including Drosophila melanogaster , Danio rerio , and Caenorhabditis elegans , the germ cell lineage is set aside from the somatic lineage very early in development.
Table 1 Symbols, names and common aliases for genes involved in mouse germ cell development and differentiation. Migration of the PGCs By 7. Bipotential germ cells in the genital ridges The genital ridges develop along the medial surface of each of the mesonephroi, two temporary nephric organs that lie either side of the dorsal mesentery. Changes in morphology and expression profile As the germ cells enter the genital ridge, major morphological and biological changes are observed, irrespective of whether germ cells are XX or XY in chromosomal constitution.
Global demethylation and chromatin remodeling Upon entry into the gonad, germ cells also undergo remarkable changes in genome methylation status and chromatin architecture. Sex determination in the germ line Upon entry into the genital ridges, the bipotential germ cells still continue to divide mitotically for 2—3 days. Choosing meiosis: do germ cells jump or are they pushed? How does RA work its magic?
Choosing meiosis in an ectopic context One of the main pieces of evidence that has been used to support the theory that germ cells are endogenously programmed to enter meiosis, and do not need to be triggered, comes from examination of rare ectopic germ cells in the mouse. If not meiosis, then what? Intrinsic changes in germ cells in the testis environment Although we do not know what triggers germ cells in a testis to stop proliferating and commit to spermatogenesis, we do have some knowledge of the molecular changes that occur in germ cells at the time of these events.
Conclusions Sex determination of the germ cell lineage, in the mammal, occurs in the gonad during fetal development. The chemical structure of proteins : a Ciba Foundation symposium. Chromatographic purification of ribonuclease and lysosyme. The partition chromatography of proteins, with particular reference to insulin and glucagon.
Peptides of ordinary tissues. On the terminal residues of chymotrypsinogen, chymotrypsings, trypsinogen and trypsin. Identification and estimation of the amide and C-terminal residues in insulin by reduction of the ester with lithium borohydride. Identification of C-end groups in proteins by reduction with lithium hydride.
Selective cleavage of peptides. Phehylisothiocyanate as a reagent for the identification of the terminal amino-acids. Specificity of certain peptidases and their use in the study of peptide and protein structure. Acyl migration in the study of protein structure. Degradation of peptides form the amino-and carboxyl ends. Protamines and nucleoprotamines. Fractionation of pepsin-catalysed hydrolysates of crystalbumin. Some speriments on the chromatographic separation and identification of peptides in partial hydrolysates of gelatin.
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