- Open Access
The function and regulation of vasa-like genes in germ-cell development
© GenomeBiology.com 2000
- Published: 1 September 2000
The vasa gene, essential for germ-cell development, was originally identified in Drosophila, and has since been found in other invertebrates and vertebrates. Analysis of these vasa homologs has revealed a highly conserved role for Vasa protein among different organisms, as well as some important differences in its regulation.
- Germ Cell
- Germ Plasm
- Germline Stem Cell
- Germ Band
- Polar Granule
In sexually reproducing organisms, primordial germ cells (PGCs) give rise to gametes that are responsible for the development of a new organism in the next generation. These cells must remain totipotent - able to differentiate into each and every cell type of all the different organs. In many organisms, maintenance of totipotency is achieved by the specification of germ cells early in embryogenesis: a small group of cells is set aside to follow a unique pathway of differentiation into gametes (reviewed in [1,2,3]).
Information on the specification of PGCs has been gained from detailed microscopical analysis, embryological experiments (for example transplantation of cells or cytoplasm) and gene identification through genetic screens for maternal-effect mutations in Drosophila and Caenorhabditis elegans (reviewed in [1,2,3,4]). The main conclusion from these two invertebrate model organisms is that asymmetrical localization of cytoplasmic determinants - the germ plasm - is responsible for the early specification of the germline lineage. The importance of localized cytoplasmic determinants for germ-cell development has been most clearly shown in Drosophila. Here, for example, cytoplasmic germ plasm determinants concentrated at the posterior pole of the embryo in 'pole plasm' can direct cells towards a germ-cell fate when transplanted to an ectopic location. In mutants in which the formation of this morphologically characteristic cytoplasm is disrupted, germ-cell formation is impaired (reviewed in ). The pole plasm is characterized by the presence of the polar granules, electron-dense structures not delimited by a membrane that contain many RNAs and proteins and that are associated with mitochondria. The distribution of the pole plasm correlates with the site of PGC formation. On the basis of their unique morphology, germ plasm components have also been identified in other organisms such as C. elegans (where they are termed P granules), Xenopus laevis (germinal granules), chick and zebrafish [1,2,3,6,7,8,9].
The specification of the germline is different in mammals. Several lines of evidence argue that here inherited cytoplasmic factors do not have a role in germ-cell specification, but that germ cells are induced through cellular interactions during gastrulation (reviewed in [1,2,3]). Morphologically distinct germ plasm has not so far been identified in early mammalian embryos. In addition, mouse eggs from which the animal or vegetal pole was experimentally removed developed into fertile mice, arguing against any polarity in the egg that is functionally important for germ-cell specification . Mouse germ cells arise just before and during early gastrulation, around the proximal part of the epiblast adjacent to the extra-embryonic region. Transplantation experiments showed that, at these stages, these cells are not yet committed to the germline, and when grafted into distal positions they can develop into somatic tissues [1,2]. Consistent with the notion of germ-cell induction through cell-cell interactions, distal cells that would develop as somatic cells can develop into germ cells when grafted into the region where germ cells normally form [1,2]. Indeed, formation of the founding population of PGCs in the mouse was shown to depend on the function of at least one extracellular factor - bone morphogentic protein 4 (Bmp4) .
Some of the methodologies used in the invertebrate models cannot be applied to vertebrates. In particular, the maternal-effect screens that were instrumental in analyzing the specification of PGCs in invertebrates are not practicable in the frog, chick or mouse. Fortunately, such screens can be carried out in the zebrafish , although in this system too, it would be very difficult to achieve saturation for all maternal-effect mutations involved in PGC specification using classical 'forward' genetic analysis.
The vasa gene was originally identified in Drosophila as a maternal-effect gene required for the formation of the abdominal segments and for germ-cell specification . The Vasa protein can be detected in the germline cells of Drosophila throughout their development and in early embryos it is specifically localized to polar granules, which are located where the germ cells are specified. Drosophila embryos that inherit mutant maternal vasa RNA and protein fail to form germ cells, and females carrying null mutations in vasa display a range of defects in oogenesis. The vasa gene encodes an ATP-dependent RNA helicase of the DEAD-box family and is required for promoting translation of at least two known mRNAs, nanos and gurken [13,14,15,16,17,18,19].
Following the isolation of the Drosophila vasa gene, vasa-like DEAD-box RNA helicase genes that are expressed in germ cells were identified in many species, including mouse, rat, frog, zebrafish, medaka (Oryzias latipes), trout, planarian, chick, ascidian, nematode, silkworm, human and the flour beetle (Table 1; [8,20,21,22,23,24,25,26,27,28,29,30], and R. Schröder and D. Tautz, personal communication). The distribution of vasa RNA or protein was determined during different stages of development, thus providing information on the possible function of vasa during germ-cell development in these species. The vasa loss-of-function phenotype in the fly, the mouse and the nematode provided direct evidence for the role of vasa in the development of germ cells in these organisms. And in cases where the origin and precise route of germ-cell migration towards the gonad were unknown (for example in fish, chick and ascidians), it proved possible, using vasa as a molecular marker, to trace back the migration path and establish the position in which these cells originate [8,23,27,31].
As can be seen from Table 1, vasa RNA is expressed in the germ cells of many organisms. But translational control, post-translational control and subcellular localization of the Vasa protein, as well as interaction with other proteins, appear to play a major part in controlling Vasa function. For example, vasa RNA is uniformly distributed in early Drosophila embryos but, consistent with its function, the protein is found localized to the posterior pole, where it is associated with the polar granules in the germ plasm. Similar discrepancies between RNA and protein expression, in which the Vasa protein is found in a restricted number of cells relative to the RNA and is localized to specific subcellular structures, have also been described in Xenopus and the nematode.
A recent thorough analysis of the distribution of the vasa gene products in zebrafish revealed a unique and surprising difference between the localization of RNA and that of the protein . The RNA is localized through a microtubule-dependent process in a novel pattern to the first and second cleavage planes of the early zebrafish embryo [23,32]. Knaut et al.  also showed that the vasa RNA aggregates reside within an electron-dense matrix similar to structures associated with germ plasm in other organisms. The localization of vasa RNA to the germ plasm allowed them to follow precisely the distribution of the germ plasm to the cells of the early embryo . Until late blastula stages, the four cells that contain germ plasm divide asymmetrically, so that only one of the blastomeres resulting from each division inherits the germ plasm labeled by vasa RNA; these will become the future PGCs. Towards the end of the blastula stage, the RNA fills the cytoplasm of the vasa-positive cells and is inherited by both daughter cells after cell division. The distribution of the Vasa protein at these early stages of development differed from that of the RNA in a striking and unexpected manner. When the vasa RNA is asymmetrically segregating to the future PGCs, the Vasa protein is uniformly distributed in the cytoplasm of all blastomeres. This initial pattern of protein expression changes at late blastula stages, when stronger protein expression is detected in the germ cells, which now divide symmetrically. At this time, the distribution of the protein within the cells becomes perinuclear.
Given that Vasa protein is implicated in establishing functional germ plasm and in the specification of germ cells in other organisms, the findings in zebrafish seem paradoxical. In Drosophila, for example, loss-of-function mutations in vasa that affect the formation of the pole plasm were shown to affect either the biochemical activity of the protein or its localization . In zebrafish, on the other hand, the vasa RNA, rather than the protein, is initially localized to the germ plasm. There are several possible explanations for this paradox. One is that in zebrafish it is the vasa RNA and not the protein that is important for the early determination of germ plasm. It is important to note, however, that in zebrafish, vasa RNA expressed ectopically during embryogenesis is unable by itself to alter the number or position of the PGCs . Furthermore, cloning of the medaka vasa homolog and analysis of its expression pattern showed that in this fish, which like the zebrafish is also a teleost, the RNA is uniformly expressed until gastrulation, when germ-cell-specific expression is observed .
Another possible explanation of the paradox is that although most of the Vasa protein is uniformly distributed in all cells, it is active only in the germ cells, as a result of cell-specific post-translational modifications. Vasa activity can indeed be affected by post-translational modification, as described during oogenesis in Drosophila . Finally, there could be a higher concentration of Vasa protein in germ cells as a result of translation of the maternally localized RNA. In this scenario, localization of vasa RNA, and presumably other RNAs, important for germ-cell determination, generates high levels of these proteins in some cells, thereby inducing the zygotic PGC differentiation path. An interesting recent discovery was recently made by Schröder and Tautz, who cloned a vasa-like gene from the 'short germ band' beetle, whose embryogenesis represents a more ancestral form of embryogenesis in insects. Tribolium castaneum (R. Schröder and D. Tautz, personal communication). They found that the distribution of vasa RNA in this insect is more reminiscent of that in zebrafish rather than the 'long germ band' Drosophila. After early uniform distribution of the RNA, the Tribolium vasa RNA appears to be located exclusively at the posterior of the early embryo, where the germ cells presumably form.
The function of the vasa gene can be inferred from its expression pattern in different organisms and from phenotypic analysis of animals lacking a functional gene. With the exception of the mouse (and probably other mammals), the vasa gene product is expressed in or localized to the PGCs very early in development, consistent with the idea that its activity is required for specification of this cell lineage. Interestingly, in planarians, where a vasa homolog is also expressed in the soma, the somatic cells that express the gene were identified as neoblasts - a totipotent cell type that functions in regeneration. The function of vasa could therefore be described as important for preserving totipotency. One mechanism for preserving totipotency is to inhibit expression of genes that would lead to somatic differentiation . An indirect role for vasa in transcriptional inhibition is suggested by the finding that one of the few known targets of Vasa, nanos, can repress gene expression in the Drosophila germline [15,35,36].
In the mouse, where germ cells are induced through cellular interactions rather than by inheritance of maternal cytoplasmic determinants, the expression of vasa is initiated relatively late [20,37]. Vasa is expressed in the PGCs as they arrive at the gonad, and expression is induced by interaction between the germ cells and the somatic cells of the developing gonad . The expression of vasa at this stage in the mouse, as well as in all the other organisms described above, is likely to reflect a requirement for the gene product for differentiation of the germ cells into gametes. Indeed, loss of vasa function in the mouse affects differentiation of the male germ cells, resulting in male sterility (no other phenotype is observed in the knockout mice) . Similarly, a late function of vasa during gametogenesis has been described in the nematode and the fly [16,17,28,33]. The first mechanistic evidence coupling progression in gamete differentiation and vasa function is the demonstration that a meiotic checkpoint during oogenesis in Drosophila appears to control the activity of the Vasa protein .
To gain a more comprehensive understanding of germline development in different species, one would obviously seek to identify most or all of the components relevant to the process and determine the functional relationships between them. Genome sequencing and the availability of expressed sequence tag (EST) libraries now allow us to identify homologs through database screens of different organisms. Isolation of new genes essential for germ-cell development is more demanding. Classical genetic analyses in invertebrates and in zebrafish are likely to identify new genes and proteins. This approach will fail, however, where there is functional redundancy among genes or when a zygotic requirement for the gene complicates the analysis of its function as a maternal factor. By using DNA microarray chips and tissue-specific probes, on the other hand, one could identify genes that are specifically expressed in the germ cells. The yeast two-hybrid system can be used to reveal new proteins that physically interact with previously identified gene products (see ). In addition, screening cDNA libraries by in situ hybridization can identify new genes even if they are expressed in other cell types as well as in germ cells. This approach has led to identification of many homologs of known genes in the zebrafish, as well as of new genes and proteins that are expressed in the germline (C. Thisse, B. Thisse and E.R., unpublished observations). Functional analysis of zebrafish genes isolated by such 'reverse' genetics approaches can be carried out using morpholino antisense oligonucleotides , which inhibit translation of their specific mRNAs in this organism (S. Ekker, personal communication).
Expression and function of vasa homologs*
Fruit fly (Drosophila melanogaster)
Early embryo: uniform, followed by specific expression in germ cells. Ovary: uniform in nurse cells and oocyte. Testis: early stage spermatocytes and germline stem cells.
Germ cells: as soon as they form and throughout embryonic development. Ovary: germline stem cells, nurse cells, oocytes. Testis: early stages of spermatogenesis.
Oocyte and cleavage-stage embryos: in polar granules, nuclear bodies and dense cytoplasmic masses.
Early embryogenesis: abdomen development, nanos mRNA translation, formation of pole plasm and germ cells. Oogenesis: germline cyst development, oocyte differentiation, gurken mRNA translation, oocyte polarity, translation of oskar mRNA.
Mouse (Mus musculus)
Testis: spermatocytes and early spermatids. Ovary: ND
Germ cells: as they arrive at thethe genital ridge. Ovary: early stages of oogenesis. Decreases during maturation. Not detected in mature oocytes. Testis: in spermatogonium to round spermatid stages.
Granules near nucleus in pachytene-diplotene spermatocytes. After meiosis: a large perinuclear granule up to spermatid nucleus elongation. Sperm: corresponds to that of the 'chromatoid body'.
Testis: required in PGCs during premeiotic stages of spermatogenesis for sperm differentiation before pachytene spermatocyte stage. Male mutants: PGC proliferation defects. Female mutants: fertile and show no defects of oogenesis.
Zebrafish (Danio rerio)
Maternally supplied to embryo. From the 32-cell stage, detected in four blastomeres. Gastrulation: expressed in four PGC clusters as they migrate towards the gonad. Testis: spermatogenesis, excluding mature spermatozoa. Ovary: all stages of oogenesis.
One-cell embryo: ring between yolk and cytoplasm. Two- to four-cell embryo: near cleavage furrow, inherited by four cells. Then asymmetrically localized and distributed between dividing blastomeres until late blastula, when it fills PGCs' cytoplasm. Late oogenesis: oocyte cortex.
Maternal protein uniformly distributed during blastula stages. At late blastula, distinct expression in PGCs as expression in somatic cells decreases.
Associated with germinal vesicle in early oogenesis. From late blastula on, associated with nuclear envelope in a pattern distinct from that of the RNA.
Planarian (Dugesia japonica)
Testis: DjvlgA in spermatogonia, spermatocytes, spermatids. DjvlgB only in spermatocytes. Ovary: both expressed in oocytes. Outside gonad DjvlgA expressed in totipotent neoblasts.
Frog (Xenopus laevis)
Gonad in both sexes. Ovary: all stages of oogenesis. Gastrulation: PGC-specific expression.
Oocytes and unfertilized eggs. Blastula and gastrula: all cells, intensity of staining decreasing with time. After gastrulation: level increases in PGCs.
Embryos: appears to be perinuclear.
Chick (Gallus gallus)
Testis: spermatogonia to mature spermatocytes. Ovary: ND
Embryos: maternal protein from the one-cell stage. Before gastrulation: Cvh-positive PGCs in center of area pellucida. Migrating and post-migratory PGCs. Testis: spermatogonia to round spermatids. Ovary: immature oocytes.
Cleaving embryos: basal part of cleavage furrows.Testis: granular staining in spermatocytes. Ovary: underneath plasma membrane, near germ-plasm-associated organelles and molecules such as mitochondria and spectrin.
Ascidian (Ciona intestinalis)
Embryo: mesenchymal cells and posterior cells presumed to be germ cells. Ovary: early oogonic cells. Testis: early spermatogenic cells.
Early embryos: posterior during two- to four-cell stage, inherited by presumed germ cells.
Nematode (Caenorhabditis elegans)
glh-1, glh-2, glh-3 and glh-4 expressed in all cells of early cleavage stages followed by a decrease to background levels. All expressed in germline cells in male and hermaphrodite.
All expressed throughout life, first in germline blastomeres and later in germ cells in gonad.
All localized to P-granules that segregate to germline blastomeres. Granules are cytoplasmic in oocyte and early embryo and perinuclear at later stages.
G1h-1, g1h-2 and g1h-4 products are required for germ-cell proliferation and gametogenesis. Oogenesis and spermatogenesis defective in glh-1/4(RNAi), with many cells not proceeding beyond pachytene.
Human (Homo sapiens)
In the fetus and adult, gonad-specific expression in both sexes.
Germ cells: expressed in PGCs as they populate the gonadal ridge as well as in PGCs that have not yet reached this target. Testis: spermatogonia, spermatocysts and spermatids. Ovary: oocytes.
Testis: granular staining in spermatocytes. Ovary: in fetal oocytes: within a compact perinuclear body. In adult oocytes no subcellular localization.
ND: hereditary infertility syndromes that map to the chromosomal region of VASA have not yet been found.
I thank Randy Cassada, Holger Knaut, Michal Reichman and Gilbert Weidinger for comments on the manuscript. The work in my lab is supported by grants from the Deutsche Forschungsgemeinschaft (DFG).
- Saffman E, Lasko P: Germline development in vertebrates and invertebrates. Cell Mol Life Sci. 1999, 55: 1141-1163. 10.1007/s000180050363.PubMedView ArticleGoogle Scholar
- Wylie C: Germ cells. Cell. 1999, 96: 165-174.PubMedView ArticleGoogle Scholar
- Wylie C: Germ cells. Curr Opin Genet Dev. 2000, 10: 410-413. 10.1016/S0959-437X(00)00105-2.PubMedView ArticleGoogle Scholar
- Williamson A, Lehmann R: Germ cell development in Drosophila. Annu Rev Cell Dev Biol. 1996, 12: 365-391. 10.1146/annurev.cellbio.12.1.365.PubMedView ArticleGoogle Scholar
- Rongo C, Lehmann R: Regulated synthesis, transport and assembly of the Drosophila germ plasm. Trends Genet. 1996, 12: 102-109. 10.1016/0168-9525(96)81421-1.PubMedView ArticleGoogle Scholar
- Braat A, Zandbergen T, van de Water S, Goos H, Zivkovic D: Characterization of zebrafish primordial germ cells: morphology and early distribution of vasa RNA. Dev Dyn. 1999, 216: 153-167. 10.1002/(SICI)1097-0177(199910)216:2<153::AID-DVDY6>3.3.CO;2-T.PubMedView ArticleGoogle Scholar
- Pitt J, Schisa J, Priess J: P granules in the germ cells of Caenorhabditis elegans adults are associated with clusters of nuclear pores and contain RNA. Dev Biol. 2000, 219: 315-333. 10.1006/dbio.2000.9607.PubMedView ArticleGoogle Scholar
- Tsunekawa N, Naito M, Sakai Y, Nishida T, Noce T: Isolation of chicken vasa homolog gene and tracing the origin of primordial germ cells. Development. 2000, 127: 2741-2750.PubMedGoogle Scholar
- Knaut H, Pelegri F, Bohmann K, Schwarz H, Nusslein-Volhard C: Zebrafish vasa RNA but not its protein is a component of the germ plasm and segregates asymmetrically before germline specification. J Cell Biol. 2000, 149: 875-888. 10.1083/jcb.149.4.875.PubMedPubMed CentralView ArticleGoogle Scholar
- Zernicka-Goetz M: Fertile offspring derived from mammalian eggs lacking either animal or vegetal poles. Development. 1998, 125: 4803-4808.PubMedGoogle Scholar
- Pelegri F, Schulte-Merker S: A gynogenesis-based screen for maternal-effect genes in the zebrafish, Danio rerio. Methods Cell Biol. 1999, 60: 1-20.PubMedView ArticleGoogle Scholar
- Schupbach T, Wieschaus E: Maternal-effect mutations altering the anterior-posterior pattern of the Drosophila embryo. Roux's Arch Dev. Biol. 1986, 195: 302-317.View ArticleGoogle Scholar
- Hay B, Jan L, Jan Y: A protein component of Drosophila polar granules is encoded by vasa and has extensive sequence similarity to ATP-dependent helicases. Cell. 1988, 55: 577-587.PubMedView ArticleGoogle Scholar
- Lasko P, Ashburner M: The product of the Drosophila gene vasa is very similar to eukaryotic initiation factor-4A. Nature. 1988, 335: 611-617. 10.1038/335611a0.PubMedView ArticleGoogle Scholar
- Gavis E, Lunsford L, Bergsten S, Lehmann R: A conserved 90 nucleotide element mediates translational repression of nanos RNA. Development. 1996, 122: 2791-2800.PubMedGoogle Scholar
- Styhler S, Nakamura A, Swan A, Suter B, Lasko P: vasa is required for GURKEN accumulation in the oocyte, and is involved in oocyte differentiation and germline cyst development. Development. 1998, 125: 1569-1578.PubMedGoogle Scholar
- Tomancak P, Guichet A, Zavorszky P, Ephrussi A: Oocyte polarity depends on regulation of gurken by Vasa. Development. 1998, 125: 1723-1732.PubMedGoogle Scholar
- Liang L, Diehl-Jones W, Lasko P: Localization of vasa protein to the Drosophila pole plasm is independent of its RNA-binding and helicase activities. Development. 1994, 120: 1201-1211.PubMedGoogle Scholar
- Carrera P, Johnstone O, Nakamura A, Casanova J, Jackle H, Lasko P: VASA mediates translation through interaction with a Drosophila ylF2 homolog. Mol Cell . 2000, 5: 181-187.PubMedView ArticleGoogle Scholar
- Fujiwara Y, Komiya T, Kawabata H, Sato M, Fujimoto H, Furusawa M, Noce T: Isolation of a DEAD-family protein gene that encodes a murine homolog of Drosophila vasa and its specific expression in germ cell lineage. Proc Natl Acad Sci USA . 1994, 91: 12258-12262.PubMedPubMed CentralView ArticleGoogle Scholar
- Komiya T, Tanigawa Y: Cloning of a gene of the DEAD box protein family which is specifically expressed in germ cells in rats. Biochem Biophys Res Commun. 1995, 207: 405-410. 10.1006/bbrc.1995.1202.PubMedView ArticleGoogle Scholar
- Komiya T, Itoh K, Ikenishi K, Furusawa M: Isolation and characterization of a novel gene of the DEAD box protein family which is specifically expressed in germ cells of Xenopus laevis. Dev Biol . 1994, 162: 354-563. 10.1006/dbio.1994.1093.PubMedView ArticleGoogle Scholar
- Yoon C, Kawakami K, Hopkins N: Zebrafish vasa homologue RNA is localized to the cleavage planes of 2- and 4-cell-stage embryos and is expressed in the primordial germ cells. Development. 1997, 124: 3157-3165.PubMedGoogle Scholar
- Shinomiya A, Tanaka M, Kobayashi T, Nagahama Y, Hamaguchi S: The vasa-like gene, olvas, identifies the migration path of primordial germ cells during embryonic body formation stage in the medaka, Oryzias latipes. Dev Growth Differ. 2000, 42: 317-326. 10.1046/j.1440-169X.2000.00521.x.PubMedView ArticleGoogle Scholar
- Yoshizaki G, Sakatani S, Tominaga H, Takeuchi T: Cloning and characterization of a vasa-like gene in rainbow trout and its expression in the germ cell lineage. Mol Reprod Dev. 2000, 55: 364-371. 10.1002/(SICI)1098-2795(200004)55:4<364::AID-MRD2>3.3.CO;2-#.PubMedView ArticleGoogle Scholar
- Shibata N, Umesono Y, Orii H, Sakurai T, Watanabe K, Agata K: Expression of vasa(vas)-related genes in germline cells and totipotent somatic stem cells of planarians. Dev Biol. 1999, 206: 73-87. 10.1006/dbio.1998.9130.PubMedView ArticleGoogle Scholar
- Fujimura M, Takamura K: Characterization of an ascidian DEAD-box gene, Ci-DEAD I: specific expression in the germ cells and its mRNA localization in the posterior-most blastomeres in early embryos. Dev Genes Evol. 2000, 210: 64-72. 10.1007/s004270050012.PubMedView ArticleGoogle Scholar
- Kuznicki K, Smith P, Leung-Chiu W, Estevez A, Scott H, KL B: Combinatorial RNA interference indicates GLH-4 can compensate for GLH-1; these two P granule components are critical for fertility in C. elegans. Development. 2000, 127: 2907-2916.PubMedGoogle Scholar
- Nakao H: Isolation and characterization of a Bombyx vasa-like protein. Dev Genes Evol. 1999, 209: 312-316. 10.1007/s004270050257.PubMedView ArticleGoogle Scholar
- Castrillon DH, Quade BJ, Wang TY, Quigley C, Crum CP: The human VASA gene is specifically expressed in the germ cell lineage. Proc Natl Acad Sci USA. 2000,Google Scholar
- Weidinger G, Wolke U, Koprunner M, Klinger M, Raz E: Identification of tissues and patterning events required for distinct steps in early migration of zebrafish primordial germ cells. Development. 1999, 126: 5295-5307.PubMedGoogle Scholar
- Pelegri F, Knaut H, Maischein H, Schulte-Merker S, Nusslein-Volhard C: A mutation in the zebrafish maternal-effect gene nebel affects furrow formation and vasa RNA localization. Curr Biol. 1999, 9: 1431-1440. 10.1016/S0960-9822(00)80112-8.PubMedView ArticleGoogle Scholar
- Ghabrial A, Schupbach T: Activation of a meiotic checkpoint regulates translation of Gurken during Drosophila oogenesis. Nat Cell Biol. 1999, 1: 354-357. 10.1038/14046.PubMedView ArticleGoogle Scholar
- Seydoux G, Strome S: Launching the germline in Caenorhabditis elegans: regulation of gene expression in early germ cells. Development. 1999, 126: 3275-3283.PubMedGoogle Scholar
- Deshpande G, Calhoun G, Yanowitz J, Schedl P: Novel functions of nanos in downregulating mitosis and transcription during the development of the Drosophila germline. Cell. 1999, 99: 271-281.PubMedView ArticleGoogle Scholar
- Parisi M, Lin H: Translational repression: a duet of Nanos and Pumilio. Curr Biol. 2000, 10: R81-R83. 10.1016/S0960-9822(00)00283-9.PubMedView ArticleGoogle Scholar
- Toyooka Y, Tsunekawa N, Takahashi Y, Matsui Y, Satoh M, Noce T: Expression and intracellular localization of mouse vasa-homologue protein during germ cell development. Mech Dev . 2000, 93: 139-149. 10.1016/S0925-4773(00)00283-5.PubMedView ArticleGoogle Scholar
- Tanaka S, Toyooka Y, Akasu R, Katoh-Fukui Y, Nakahara Y, Suzuki R, Yokoyama M, Noce T: The mouse homolog of Drosophila Vasa is required for the development of male germ cells. Genes Dev. 2000, 14: 841-853.PubMedPubMed CentralGoogle Scholar
- Summerton J, Weller D: Morpholino antisense oligomers:design, preparation, and properties. Antisense Nucleic Acid Drug Dev. 1997, 7: 187-195.PubMedView ArticleGoogle Scholar
- Hay B, Ackerman L, Barbel S, Jan L, Jan Y: Identification of a component of Drosophila polar granules. Development. 1988, 103: 625-640.PubMedGoogle Scholar
- Markussen F, Michon A, Breitwieser W, Ephrussi A: Translational control of oskar generates short OSK, the isoform that induces pole plasma assembly. Development. 1995, 121: 3723-3732.PubMedGoogle Scholar
- Ikenishi K, Tanaka T, Komiya T: Spatio-temporal distribution of the protein of the Xenopus vasa homologue (Xenopus vasa-like gene I, XVLGI) in embryos. Dev Growth Differ. 1996, 38: 527-535. 10.1046/j.1440-169X.1996.t01-4-00009.x.View ArticleGoogle Scholar
- Ikenishi K, Tanaka T: Involvement of the protein of Xenopus vasa homolog (Xenopus vasa-like gene I, XVLGI) in the differentiation of primordial germ cells. Dev Growth Differ. 1997, 39: 625-633. 10.1046/j.1440-169X.1997.t01-4-00010.x.PubMedView ArticleGoogle Scholar
- Ikenishi K, Tanaka T: Spatio-temporal expression of Xenopus vasa homolog, XVLGI, in oocytes and embryos: the presence of XVLGI RNA in somatic cells as well as germline cells. Dev Growth Differ. 2000, 42: 95-103. 10.1046/j.1440-169X.2000.00493.x.PubMedView ArticleGoogle Scholar
- Gruidl M, Smith P, Kuznicki K, McCrone J, Kirchner J, Roussell D, et al: Multiple potential germ-line helicases are components of the germ-line-specific P granules of Caenorhabditis elegans. Proc Natl Acad Sci USA. 1996, 93: 13837-13842. 10.1073/pnas.93.24.13837.PubMedPubMed CentralView ArticleGoogle Scholar