Genomes and Genes
Gene Symbol: Ddx4
Description: DEAD (Asp-Glu-Ala-Asp) box polypeptide 4
Alias: AV206478, Mvh, VASA, ATP-dependent RNA helicase DDX4, D-E-A-D (aspartate-glutamate-alanine-aspartate) box polypeptide 4, DEAD (aspartate-glutamate-alanine-aspartate) box polypeptide 4, DEAD box polypeptide 4, DEAD box protein 4, DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 4, mvh / m'vasa, vasa homolog
- Tanaka S, Toyooka Y, Akasu R, Katoh Fukui Y, Nakahara Y, Suzuki R, et al. The mouse homolog of Drosophila Vasa is required for the development of male germ cells. Genes Dev. 2000;14:841-53 pubmedRestricted expression of a mouse Vasa homolog gene (Mvh) expression is first detected in primordial germ cells (PGCs) after colonization of the genital ridges. Subsequently, Mvh is maintained until postmeiotic germ cells are formed...
- Hayashi K, Yoshida K, Matsui Y. A histone H3 methyltransferase controls epigenetic events required for meiotic prophase. Nature. 2005;438:374-8 pubmed..These findings indicate that meiosis-specific epigenetic events in mammals are crucial for proper meiotic progression. ..
- Kimura T, Suzuki A, Fujita Y, Yomogida K, Lomeli H, Asada N, et al. Conditional loss of PTEN leads to testicular teratoma and enhances embryonic germ cell production. Development. 2003;130:1691-700 pubmed..PTEN appears to be essential for germ cell differentiation and an important factor in testicular germ cell tumor formation. ..
- Kuramochi Miyagawa S, Kimura T, Ijiri T, Isobe T, Asada N, Fujita Y, et al. Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Development. 2004;131:839-49 pubmed..Furthermore, MILI bound to MVH, which is an essential factor during the early spermatocyte stage...
- Medeiros L, Dennis L, Gill M, Houbaviy H, Markoulaki S, Fu D, et al. Mir-290-295 deficiency in mice results in partially penetrant embryonic lethality and germ cell defects. Proc Natl Acad Sci U S A. 2011;108:14163-8 pubmed publisher..Female mir-290-295(-/-) mice are unable to recover and are sterile, due to premature ovarian failure. ..
- Tachibana M, Nozaki M, Takeda N, Shinkai Y. Functional dynamics of H3K9 methylation during meiotic prophase progression. EMBO J. 2007;26:3346-59 pubmed..This genetic and biochemical evidence strongly suggests that a specific set of H3K9 methyltransferase(s) and demethylase(s) coordinately regulate gametogenesis. ..
- Lin Y, Page D. Dazl deficiency leads to embryonic arrest of germ cell development in XY C57BL/6 mice. Dev Biol. 2005;288:309-16 pubmed..By E14.5, expression of germ cell markers (Mvh, Oct4, Dppa3/Stella, GCNA and MVH protein) was reduced in XY Dazl-/- gonads. By E15...
- Suzuki A, Igarashi K, Aisaki K, Kanno J, Saga Y. NANOS2 interacts with the CCR4-NOT deadenylation complex and leads to suppression of specific RNAs. Proc Natl Acad Sci U S A. 2010;107:3594-9 pubmed publisher..We propose from our current findings that NANOS2-interacting RNAs may be recruited to P-bodies and degraded by the enzymes contained therein through NANOS2-mediated deadenylation. ..
- Kotaja N, Bhattacharyya S, Jaskiewicz L, Kimmins S, Parvinen M, Filipowicz W, et al. The chromatoid body of male germ cells: similarity with processing bodies and presence of Dicer and microRNA pathway components. Proc Natl Acad Sci U S A. 2006;103:2647-52 pubmed..we show that Dicer interacts with a germ cell-specific chromatoid body component, the RNA helicase MVH (mouse VASA homolog). Thus, chromatoid bodies seem to operate as intracellular nerve centers of the microRNA pathway...
- Maatouk D, Kellam L, Mann M, Lei H, Li E, Bartolomei M, et al. DNA methylation is a primary mechanism for silencing postmigratory primordial germ cell genes in both germ cell and somatic cell lineages. Development. 2006;133:3411-8 pubmed..Here, we show that the postmigratory germ cell-specific genes Mvh, Dazl and Scp3 are demethylated in germ cells, but not in somatic cells...
- MacLean G, Li H, Metzger D, Chambon P, Petkovich M. Apoptotic extinction of germ cells in testes of Cyp26b1 knockout mice. Endocrinology. 2007;148:4560-7 pubmed..These results provide evidence that CYP26B1 maintains low levels of RA in the developing testes that blocks entry into meiosis and acts as a survival factor to prevent apoptosis of male germ cells. ..
- McClellan K, Gosden R, Taketo T. Continuous loss of oocytes throughout meiotic prophase in the normal mouse ovary. Dev Biol. 2003;258:334-48 pubmed..A recent study using Mouse Vasa Homologue (MVH) as a germ cell marker reached a contradictory conclusion claiming that oocyte loss occurs in the ..
- Cook M, Coveney D, Batchvarov I, Nadeau J, Capel B. BAX-mediated cell death affects early germ cell loss and incidence of testicular teratomas in Dnd1(Ter/Ter) mice. Dev Biol. 2009;328:377-83 pubmed publisher..We conclude that BAX-mediated apoptosis plays a role in early germ cell loss and protects from testicular teratoma formation on a mixed genetic background...
- Saxe J, Chen M, Zhao H, Lin H. Tdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline. EMBO J. 2013;32:1869-85 pubmed publisher..These results shed light on mechanisms underlying primary piRNA biogenesis, an area in which information is conspicuously absent. ..
- 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...
- Chuma S, Hosokawa M, Kitamura K, Kasai S, Fujioka M, Hiyoshi M, et al. Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell differentiation and nuage/germinal granule formation in mice. Proc Natl Acad Sci U S A. 2006;103:15894-9 pubmed..structure in the germ line, and its intracellular localization is downstream of mouse vasa homologue/DEAD box polypeptide 4 (Mvh/Ddx4), similar to Drosophila vasa-tudor...
- De Fazio S, Bartonicek N, Di Giacomo M, Abreu Goodger C, Sankar A, Funaya C, et al. The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature. 2011;480:259-63 pubmed publisher..In addition, the hallmarks of piRNA amplification are observed in Miwi2-deficient gonadocytes. We conclude that cycles of intra-Mili secondary piRNA biogenesis fuel piRNA amplification that is absolutely required for LINE1 silencing. ..
- Hosokawa M, Shoji M, Kitamura K, Tanaka T, Noce T, Chuma S, et al. Tudor-related proteins TDRD1/MTR-1, TDRD6 and TDRD7/TRAP: domain composition, intracellular localization, and function in male germ cells in mice. Dev Biol. 2007;301:38-52 pubmed..The characteristic co-localization of TDRD1, 6 and 7 was disrupted in a mutant of mouse vasa homologue/DEAD box polypeptide 4 (Mvh/Ddx4), which encodes another evolutionarily conserved component of nuage...
- Ma L, Buchold G, Greenbaum M, Roy A, Burns K, Zhu H, et al. GASZ is essential for male meiosis and suppression of retrotransposon expression in the male germline. PLoS Genet. 2009;5:e1000635 pubmed publisher..These studies provide the first evidence for an essential structural role for GASZ in male fertility and epigenetic and post-transcriptional silencing of retrotransposons by stabilizing MILI in nuage. ..
- Fujiwara Y, Komiya T, Kawabata H, Sato M, Fujimoto H, Furusawa M, et al. 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 U S A. 1994;91:12258-62 pubmed..of the determination processes of the mammalian germ cell lineage, we have tried to isolate a mouse gene homolog to vasa, which plays an essential role as a maternal determining factor for the formation of Drosophila germ cell ..
- Dawlaty M, Ganz K, Powell B, Hu Y, Markoulaki S, Cheng A, et al. Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development. Cell Stem Cell. 2011;9:166-75 pubmed publisher..Our data suggest that Tet1 loss leading to a partial reduction in 5hmC levels does not affect pluripotency in ESCs and is compatible with embryonic and postnatal development. ..
- Pandey R, Tokuzawa Y, Yang Z, Hayashi E, Ichisaka T, Kajita S, et al. Tudor domain containing 12 (TDRD12) is essential for secondary PIWI interacting RNA biogenesis in mice. Proc Natl Acad Sci U S A. 2013;110:16492-7 pubmed publisher..Cell-culture studies with the insect ortholog of TDRD12 suggest a role for the multidomain protein in mediating complex formation with other participants during secondary piRNA biogenesis. ..
- Kuramochi Miyagawa S, Watanabe T, Gotoh K, Takamatsu K, Chuma S, Kojima Kita K, et al. MVH in piRNA processing and gene silencing of retrotransposons. Genes Dev. 2010;24:887-92 pubmed publisher..Here, we report that essentially the same abnormalities are observed in MVH (mouse VASA homolog)-deficient mice...
- Aravin A, van der Heijden G, Castañeda J, Vagin V, Hannon G, Bortvin A. Cytoplasmic compartmentalization of the fetal piRNA pathway in mice. PLoS Genet. 2009;5:e1000764 pubmed publisher..piP-bodies are found predominantly in the proximity of pi-bodies and the two frequently share mouse VASA homolog (MVH) protein, an RNA helicase...
- Spiller C, Wilhelm D, Koopman P. Retinoblastoma 1 protein modulates XY germ cell entry into G1/G0 arrest during fetal development in mice. Biol Reprod. 2010;82:433-43 pubmed publisher..proliferation was reflected with a trend of increased germ cell number and expression of germ cell markers Ddx4 and Pou5f1 in the Rb1(-/-) testes. By 16...
- 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..Collectively, our data demonstrate for the first time that some homeobox genes are required for meiosis initiation in the female germ line. ..
- Costa Y, Speed R, Gautier P, Semple C, Maratou K, Turner J, et al. Mouse MAELSTROM: the link between meiotic silencing of unsynapsed chromatin and microRNA pathway?. Hum Mol Genet. 2006;15:2324-34 pubmed..Furthermore, in the nuage, MAEL is present in a complex with germ cell specific MVH, an RNA helicase and Argonaute family members, MILI and MIWI...
- Gill M, Hu Y, Lin Y, Page D. Licensing of gametogenesis, dependent on RNA binding protein DAZL, as a gateway to sexual differentiation of fetal germ cells. Proc Natl Acad Sci U S A. 2011;108:7443-8 pubmed publisher..In C57BL/6 mice, Dazl is required for licensing. Licensing serves as a gateway from the embryonic processes shared between the sexes--germ cell specification and migration--to the sex-specific pathways of oogenesis and spermatogenesis. ..
- Shibata N, Tsunekawa N, Okamoto Ito S, Akasu R, Tokumasu A, Noce T. Mouse RanBPM is a partner gene to a germline specific RNA helicase, mouse vasa homolog protein. Mol Reprod Dev. 2004;67:1-7 pubmedGerm cell-specific ATP-dependent RNA helicase, the product of the mouse vasa homolog (Mvh), has been shown to play an essential role in the development of the male germ cell...
- Nagamori I, Cruickshank V, Sassone Corsi P. Regulation of an RNA granule during spermatogenesis: acetylation of MVH in the chromatoid body of germ cells. J Cell Sci. 2011;124:4346-55 pubmed publisherDuring mammalian spermatogenesis, the mouse VASA homolog (MVH; also known as DDX4), a germ-cell-specific DEAD-box type RNA-binding protein, localizes in a germline-specific RNA granule termed the chromatoid body (CB)...
- 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. ..
- Bradford S, Hiramatsu R, Maddugoda M, Bernard P, Chaboissier M, Sinclair A, et al. The cerebellin 4 precursor gene is a direct target of SRY and SOX9 in mice. Biol Reprod. 2009;80:1178-88 pubmed publisher..Our findings suggest that both SRY and SOX9 contribute to the male-specific upregulation of Cbln4 in the developing testis, and they identified a direct in vivo target gene of SRY. ..
- Ina S, Tsunekawa N, Nakamura A, Noce T. Expression of the mouse Aven gene during spermatogenesis, analyzed by subtraction screening using Mvh-knockout mice. Gene Expr Patterns. 2003;3:635-8 pubmedAs an attempt to investigate the function of the mouse Vasa-homolog (MVH) protein, a germ cell-specific RNA helicase, we have cloned genes that fail to be expressed in homozygous Mvh-knockout testes...
- Callier P, Calvel P, Matevossian A, Makrythanasis P, Bernard P, Kurosaka H, et al. Loss of function mutation in the palmitoyl-transferase HHAT leads to syndromic 46,XY disorder of sex development by impeding Hedgehog protein palmitoylation and signaling. PLoS Genet. 2014;10:e1004340 pubmed publisher..Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development. ..
- Arora R, Altman E, Tran N, Laird D. Novel domains of expression for orphan receptor tyrosine kinase Ror2 in the human and mouse reproductive system. Dev Dyn. 2014;243:1037-45 pubmed publisher..This study sets the stage to explore function for this tyrosine kinase receptor in novel regions of expression in the developing reproductive system in both mouse and human. ..
- Mu W, Starmer J, Shibata Y, Yee D, Magnuson T. EZH1 in germ cells safeguards the function of PRC2 during spermatogenesis. Dev Biol. 2017;424:198-207 pubmed publisher..Taken together, our findings suggest that the expression level of Ezh1 determines the restoration of H3K27 methylation in the absence of the canonical EZH2-PRC2. ..
- Xu Y, Cao L, Wang M, Xu Y, Wu X, Liu J, et al. Maternal DCAF2 is crucial for maintenance of genome stability during the first cell cycle in mice. J Cell Sci. 2017;130:3297-3307 pubmed publisher..Maternal DCAF2 protein is crucial for prevention of DNA re-replication in the first and unique mitotic cell cycle of the zygote.This article has an associated First Person interview with the first author of the paper. ..
- Gordeev O, Lifantseva N, Khaidukov S. [Expression patterns of germ line specific genes in mouse and human pluripotent stem cells are associated with regulation of ground and primed state of pluripotency]. Ontogenez. 2011;42:403-24 pubmed..5. Quantitative real time PCR analysis showed that Vasa/Ddx4 expression in mouse and human embryonic stem cells was significantly lower than in blastocyst and gonocytes...
- 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. ..
- 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..Thus DMRT1 controls Stra8 sex-specifically, activating it in the fetal ovary and repressing it in the adult testis. ..
- Xu J, Gridley T. Notch2 is required in somatic cells for breakdown of ovarian germ-cell nests and formation of primordial follicles. BMC Biol. 2013;11:13 pubmed publisher..However, no in vivo loss-of-function studies have been performed to establish whether Notch family receptors have an essential physiological role during normal ovarian development in mutant mice...
- Reynolds N, Collier B, Maratou K, Bingham V, Speed R, Taggart M, et al. Dazl binds in vivo to specific transcripts and can regulate the pre-meiotic translation of Mvh in germ cells. Hum Mol Genet. 2005;14:3899-909 pubmed..We have focussed on mouse vasa homologue (Mvh), a gene that is essential for male gametogenesis, and show that Dazl stimulates translation via the ..
- Arango N, Li L, Dabir D, Nicolau F, Pieretti Vanmarcke R, Koehler C, et al. Meiosis I arrest abnormalities lead to severe oligozoospermia in meiosis 1 arresting protein (M1ap)-deficient mice. Biol Reprod. 2013;88:76 pubmed publisher..Our results uncovered an essential role for M1ap as a novel germ cell gene not previously implicated in male germ cell development and suggest that mutations in M1AP could account for some cases of nonobstructive oligozoospermia in men. ..
- Yamashiro C, Hirota T, Kurimoto K, Nakamura T, Yabuta Y, Nagaoka S, et al. Persistent Requirement and Alteration of the Key Targets of PRDM1 During Primordial Germ Cell Development in Mice. Biol Reprod. 2016;94:7 pubmed publisher..Our findings provide critical insight into the mechanism for maintaining the transcriptional integrity of PGCs. ..
- Suzuki H, Tsuda M, Kiso M, Saga Y. Nanos3 maintains the germ cell lineage in the mouse by suppressing both Bax-dependent and -independent apoptotic pathways. Dev Biol. 2008;318:133-42 pubmed publisher..Our findings thus suggest that heterogeneity exists in the PGC populations and that Nanos3 maintains the germ cell lineage by suppressing both Bax-dependent and Bax-independent apoptotic pathways. ..
- Yamaji M, Tanaka T, Shigeta M, Chuma S, Saga Y, Saitou M. Functional reconstruction of NANOS3 expression in the germ cell lineage by a novel transgenic reporter reveals distinct subcellular localizations of NANOS3. Reproduction. 2010;139:381-93 pubmed publisher..These findings unveil the presence of distinct posttranscriptional regulations in PGCs soon after their specification, for which RNA-binding proteins such as NANOS3 and TIAL1 would play critical functions. ..
- Malki S, van der Heijden G, O Donnell K, Martin S, Bortvin A. A role for retrotransposon LINE-1 in fetal oocyte attrition in mice. Dev Cell. 2014;29:521-533 pubmed publisher..We propose that FOA serves to select oocytes with limited L1 activity that are therefore best suited for the next generation...
- Beverdam A, Svingen T, Bagheri Fam S, Bernard P, McClive P, Robson M, et al. Sox9-dependent expression of Gstm6 in Sertoli cells during testis development in mice. Reproduction. 2009;137:481-6 pubmed publisher..Our data suggest that Gstm6 plays a male-specific role in gonad development or function, possibly by modulating the exposure of somatic tissue and/or germ cells to endogenous or exogenous toxicants. ..
- Kirino Y, Vourekas A, Kim N, de Lima Alves F, Rappsilber J, Klein P, et al. Arginine methylation of vasa protein is conserved across phyla. J Biol Chem. 2010;285:8148-54 pubmed publisher..The RNA helicase Vasa is another essential protein in germline development. Here, we report that mouse (mouse Vasa homolog), Xenopus laevis, and D. melanogaster Vasa proteins contain both symmetrical and asymmetrical dimethylarginines...
- Song K, Ma W, Huang C, Ding J, Cui D, Tan X, et al. Effect and mechanism of Bushen Huoxue recipe on ovarian reserve in mice with premature ovarian failure. J Huazhong Univ Sci Technolog Med Sci. 2016;36:571-575 pubmed publisher..Meanwhile, the mRNA and protein level of Mouse Vasa Homologue (MVH) in the bone marrow, peripheral blood and ovary were detected, to explore the underlying mechanism ..
- 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. ..
- Taketo T, Lee C, Zhang J, Li Y, Lee C, Lau Y. Expression of SRY proteins in both normal and sex-reversed XY fetal mouse gonads. Dev Dyn. 2005;233:612-22 pubmed..XY gonads and was not associated with testis cord organization in B6.Y(TIR) gonads. We conclude that the testis-determining pathway is impaired at the site of SRY action in the B6.Y(TIR) gonad. ..
- Rios Rojas C, Spiller C, Bowles J, Koopman P. Germ cells influence cord formation and Leydig cell gene expression during mouse testis development. Dev Dyn. 2016;245:433-44 pubmed publisher..These observations point to the existence of germ cell-derived signals that directly or indirectly affect the Sertoli and Leydig cell populations, and provide a new paradigm for the organogenesis of the mammalian testes. ..
- Kimura T, Nakamura T, Murayama K, Umehara H, Yamano N, Watanabe S, et al. The stabilization of beta-catenin leads to impaired primordial germ cell development via aberrant cell cycle progression. Dev Biol. 2006;300:545-53 pubmed..Our results show that the suppression of Wnt/beta-catenin signaling is a prerequisite for the normal development of PGCs. ..
- Manuylov N, Zhou B, Ma Q, Fox S, Pu W, Tevosian S. Conditional ablation of Gata4 and Fog2 genes in mice reveals their distinct roles in mammalian sexual differentiation. Dev Biol. 2011;353:229-41 pubmed publisher..Our results now demonstrate that these two genes also have non-overlapping essential functions in testis development. ..
- Suzuki A, Niimi Y, Shinmyozu K, Zhou Z, Kiso M, Saga Y. Dead end1 is an essential partner of NANOS2 for selective binding of target RNAs in male germ cell development. EMBO Rep. 2016;17:37-46 pubmed publisher..We also present the first evidence that the zinc finger domain of Nanos acts as a protein-interacting domain for another RBP, providing a novel insight into Nanos-mediated germ cell development. ..
- 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. ..