Affinage

DDX4

Probable ATP-dependent RNA helicase DDX4 · UniProt Q9NQI0

Length
724 aa
Mass
79.3 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDX4 (Vasa) is a germline-specific DEAD-box RNA helicase that couples ATP hydrolysis to RNA strand separation and serves as a central organizer of germ cell identity, transposon defense, translational control, and cell division. Its crystal structure reveals that ATP binding closes two RecA-like domains around single-stranded RNA while a conserved wedge helix bends the substrate to disrupt base pairs, a mechanism validated by mutagenesis (PMID:16630817). DDX4 nucleates a piRNA amplifier complex on transposon transcripts by clamping RNA and remodeling ribonucleoprotein intermediates to transfer piRNA precursors between Piwi-family proteins, a function essential for fertility (PMID:24910301), and it activates translation of specific mRNAs such as gurken and cyclinB (PMID:9521895, PMID:21525076). Recruitment to nuage and germ granules depends on LOTUS-domain scaffold proteins (Oskar, TDRD5/7, MIP-1/2) that bind and stimulate its helicase activity (PMID:28536148, PMID:34223818), while PRMT5-mediated symmetric dimethylation of N-terminal arginines enables interactions with Tudor-domain and Piwi proteins required for spermatogenesis (PMID:20080973, PMID:36634107).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 High

    Establishing how Vasa is recruited to germ plasm: the discovery that Oskar directly binds Vasa and that this interaction is the initial nucleation step for polar granule assembly answered how germ plasm components are organized.

    Evidence Yeast two-hybrid and in vitro binding with Drosophila genetics showing mutations abolishing pole plasm also disrupt Oskar–Vasa interaction

    PMID:8804312

    Open questions at the time
    • Binding interface unresolved at this stage
    • Whether Oskar stimulates Vasa catalytic activity unknown
    • Mechanism beyond nucleation not addressed
  2. 1998 High

    Defining Vasa's role in mRNA regulation: loss-of-function analysis showed Vasa is required for translational activation of gurken mRNA and for accumulation/localization of multiple patterning mRNAs, establishing a direct link between its helicase function and mRNA-level control.

    Evidence Null and hypomorphic allele analysis in Drosophila oocytes with in situ hybridization and immunostaining for Gurken protein

    PMID:9521895 PMID:9676188

    Open questions at the time
    • Whether Vasa directly binds gurken mRNA unknown
    • Mechanism of translational activation (initiation vs. elongation) unresolved
  3. 2000 Medium

    Extending germline specificity to mammals: human DDX4 was shown to be expressed exclusively in germ cells from primordial stages through adulthood, confirming conservation of germline-restricted expression.

    Evidence Northern blot tissue panel and immunohistochemistry on fetal and adult human tissues

    PMID:10920202

    Open questions at the time
    • No functional manipulation performed in human tissue
    • Whether human DDX4 performs the same biochemical functions as Drosophila Vasa untested
  4. 2002 High

    Identifying a dedicated localization factor: Gustavus (SPRY/B30.2-domain protein) was shown to bind Vasa's N-terminus and be required for posterior Vasa localization, revealing a post-translational targeting mechanism distinct from Oskar-mediated germ plasm assembly.

    Evidence Genetic screen, direct protein interaction mapping, and loss-of-function localization phenotype in Drosophila

    PMID:12479811

    Open questions at the time
    • Mechanism by which Gustavus directs localization (trafficking vs. anchoring) unresolved
    • Whether Gustavus ubiquitin-ligase recruitment affects Vasa turnover unclear
  5. 2006 High

    Solving the catalytic mechanism: the crystal structure of Vasa's helicase core with RNA and an ATP analog revealed how ATP-driven domain closure and a wedge helix cooperate to bend and unwind RNA, providing the first atomic-resolution model for DEAD-box helicase strand separation.

    Evidence X-ray crystallography at 2.2 Å with site-directed mutagenesis and functional assays on Drosophila Vasa

    PMID:16630817

    Open questions at the time
    • Structure captured a single conformational snapshot; full catalytic cycle intermediates not resolved
    • No structure with double-stranded RNA substrate
  6. 2010 High

    Revealing post-translational regulation by arginine methylation: mass spectrometry identified symmetric and asymmetric dimethylarginine marks on Vasa deposited by PRMT5, and these marks mediate interactions with Tudor-domain proteins (Tdrd1, Tdrd6) and Piwi proteins (Mili, Miwi), linking post-translational modification to piRNA pathway complex assembly.

    Evidence Mass spectrometry identification of dimethylarginine on mouse/Drosophila Vasa, co-immunoprecipitation, dPRMT5 mutant epistasis

    PMID:20080973

    Open questions at the time
    • Which specific methylation sites are individually required for each interaction untested
    • Whether methylation regulates helicase activity directly unknown
  7. 2010 High

    Uncovering a translation-independent mitotic function: Vasa was found to associate with condensin I subunits Barren and CAP-D2 and to promote their chromosomal localization during germline mitosis, establishing a cell-cycle role beyond RNA regulation.

    Evidence Co-immunoprecipitation, loss-of-function genetics, and immunofluorescence during Drosophila germline mitosis

    PMID:21185189

    Open questions at the time
    • Whether Vasa directly remodels condensin-containing RNPs or acts indirectly through RNA unknown
    • Conservation of mitotic function in mammals not tested
  8. 2011 High

    Demonstrating conserved cell-cycle regulation: in sea urchin embryos, Vasa oscillates with the cell cycle, localizes to the mitotic spindle, and is required for cyclinB mRNA translation and chromosome segregation, extending the mitotic function beyond Drosophila.

    Evidence Morpholino knockdown, immunofluorescence for spindle association, cyclinB translation assay in sea urchin

    PMID:21525076

    Open questions at the time
    • Whether cyclinB mRNA is a direct Vasa-bound target unknown
    • Mechanism linking spindle association to translational activation unclear
  9. 2014 High

    Defining the piRNA amplifier mechanism: Vasa was shown to nucleate a multi-protein complex on transposon transcripts using its helicase domain as an RNA clamp, and ATP-dependent RNP remodeling transfers piRNA precursors between ping-pong partners Aub and AGO3, directly explaining how secondary piRNA biogenesis is catalyzed.

    Evidence Biochemical reconstitution, co-immunoprecipitation, mass spectrometry, and Drosophila ATPase-dead mutant sterility phenotype

    PMID:24910301

    Open questions at the time
    • Structural basis of the RNA-clamp conformation not resolved
    • Stoichiometry and dynamics of the amplifier complex in vivo unknown
  10. 2015 High

    Mapping domain modularity: systematic in vivo mutagenesis revealed that distinct Vasa domains (N-terminal, C-terminal 7 residues, helicase core) serve separable functions in localization, transposon repression, and pole cell specification, with many catalytic mutations not preventing nuage localization.

    Evidence Transgenic GFP-fusion domain deletion and point mutation series with functional complementation in Drosophila

    PMID:25795910

    Open questions at the time
    • Binding partners for the essential C-terminal 7 residues unidentified
    • Whether catalysis-independent functions involve passive RNA binding or scaffolding untested
  11. 2017 High

    Establishing LOTUS domains as activating cofactors: crystal structures and biochemical assays showed that LOTUS domains in Oskar, TDRD5, and TDRD7 bind Vasa's C-terminal RecA-like domain and stimulate its ATPase and helicase activities, explaining how germ granule scaffolds directly regulate Vasa enzymatic output.

    Evidence X-ray crystallography of Oskar-LOTUS/Vasa complex, in vitro helicase stimulation assays, Drosophila localization genetics

    PMID:28536148

    Open questions at the time
    • Whether LOTUS-mediated stimulation is required for all Vasa functions (piRNA, translation) untested
    • No structural information for TDRD5 or TDRD7 LOTUS domains bound to Vasa
  12. 2019 High

    Linking ATPase activity to phase-separated granule residency: in C. elegans, CRISPR-generated catalytic mutations in GLH-1/Vasa abolished P-granule localization, demonstrating that the ATPase cycle is required for partitioning into germ granule condensates, while N-terminal glycine-rich repeats promote wetting interactions.

    Evidence CRISPR/Cas9 allelic series (28 alleles), mass spectrometry interactome, live imaging in C. elegans

    PMID:31506335

    Open questions at the time
    • Whether ATPase activity drives liquid-phase partitioning or maintains it through RNA remodeling unresolved
    • Direct biophysical measurements of phase behavior not performed
  13. 2021 High

    Identifying conserved LOTUS-domain scaffolds in nematodes: MIP-1 and MIP-2 were found to bind and anchor GLH-1/Vasa within P granules and are required for coalescence of multiple germ granule components, extending the LOTUS-domain recruitment mechanism from Drosophila to C. elegans.

    Evidence Co-immunoprecipitation, CRISPR knockouts, live imaging, and protein interaction mapping in C. elegans

    PMID:34223818

    Open questions at the time
    • Whether MIP-1/2 stimulate GLH-1 ATPase activity like Drosophila LOTUS proteins untested
    • Structural basis of MIP–GLH interaction unknown
  14. 2022 High

    Connecting Vasa's ATPase cycle to small RNA pathway specificity: GLH-1's ATPase cycle was shown to regulate its direct binding to the Argonaute WAGO-1, with GLH proteins competing to control which Argonaute pathways are active, linking helicase biochemistry to transgenerational epigenetic inheritance.

    Evidence Co-immunoprecipitation, RNA-seq, and ATPase-dead mutant genetic epistasis in C. elegans

    PMID:36070689

    Open questions at the time
    • Structural basis for ATPase-dependent Argonaute binding unknown
    • Whether this competition mechanism operates in Drosophila or vertebrates untested
  15. 2023 High

    Establishing a conserved PRMT5–Vasa axis essential for spermatogenesis: in Bombyx mori, PRMT5 dimethylates Vasa at specific arginines, and CRISPR knockout of either gene produces convergent sterility with sperm defects, demonstrating that arginine methylation of Vasa is functionally required across phyla.

    Evidence CRISPR/Cas9 knockout of BmPrmt5 and BmVasa, mass spectrometry identification of R35/R54/R56 dimethylation, RNA-seq

    PMID:36634107

    Open questions at the time
    • Whether individual methylation sites have distinct functions unknown
    • Downstream Tudor-domain partners in Bombyx not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: (1) the structural basis for Vasa's RNA-clamp/amplifier complex on transposon transcripts; (2) how Vasa's catalytic versus scaffolding functions are partitioned among its diverse roles (piRNA biogenesis, translation, chromosome condensation); (3) whether the mitotic condensin-associated function is conserved in mammals; and (4) the identity of direct mRNA targets bound by Vasa in vivo across species.
  • No transcriptome-wide CLIP map of Vasa-bound RNAs across species
  • No cryo-EM structure of the piRNA amplifier complex
  • Mammalian DDX4 functional dissection largely lacking compared to invertebrate models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 4 GO:0003723 RNA binding 3 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005694 chromosome 2 GO:0005829 cytosol 2
Pathway
GO:0003723 RNA binding 3 R-HSA-1266738 Developmental Biology 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 1
Partners
AGO3AUBERGINEGUSTAVUSOSKARTDRD1TDRD5TDRD7WAGO-1
Complex memberships
P granule / nuagecondensin IpiRNA amplifier complex (Aub/AGO3/Qin)

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Crystal structure of Drosophila Vasa (DDX4 ortholog) helicase core in complex with single-stranded RNA and ATP analog revealed that ATP binding brings two RecA-like domains into a closed conformation with extensive interdomain interactions; a conserved 'wedge' helix in the N-terminal domain bends the bound RNA to disrupt base pairs, coupling ATP hydrolysis to RNA unwinding. Mutational analyses confirmed that interdomain interactions are required for this mechanism. X-ray crystallography (2.2 Å) combined with site-directed mutagenesis and functional assays Cell High 16630817
2014 Drosophila Vasa nucleates an 'Amplifier' complex on transposon transcripts to mediate secondary piRNA biogenesis. Vasa's helicase domain functions as an RNA clamp to anchor the complex (containing Piwi proteins Aub and AGO3, Tudor protein Qin/Kumo, and antisense piRNA guides) onto transposon transcripts, and ATP-dependent RNP remodeling by Vasa facilitates transfer of 5'-sliced piRNA precursors between ping-pong partners. Loss of this ATPase activity causes sterility. Co-immunoprecipitation, mass spectrometry, biochemical reconstitution, Drosophila genetics (sterility phenotype with ATPase-dead mutants) Cell High 24910301
2015 The N-terminal LOTUS domain of Oskar forms dimers and mediates direct interaction with the germline-specific RNA helicase Vasa in vitro; crystal structures of the Oskar LOTUS domain alone and in complex with the C-terminal RecA-like domain of Vasa were solved, revealing the molecular basis of this interaction essential for germ plasm assembly. X-ray crystallography, in vitro binding assays, RNA crosslinking Cell Reports High 26190108
2017 LOTUS domains present in Oskar, TDRD5, and TDRD7 directly bind and stimulate the ATPase/helicase activity of Vasa. Crystal structure of the Oskar LOTUS domain in complex with the C-terminal RecA-like domain of Vasa reveals a novel regulatory surface on the helicase. In vivo, localization of Drosophila Vasa to nuage and germ plasm requires its interaction with LOTUS-domain proteins. X-ray crystallography, in vitro helicase stimulation assays, Drosophila genetics (localization phenotypes) Genes & Development High 28536148
1996 Oskar protein directly interacts with Vasa in yeast two-hybrid assays and in vitro, and this interaction is required for polar granule assembly in Drosophila. Mutations in Oskar that abolish pole plasm formation in vivo also disrupt the Oskar-Vasa interaction, identifying the Oskar-Vasa interaction as an initial step in polar granule assembly. Yeast two-hybrid, in vitro binding assay, in vivo genetics Genes & Development High 8804312
2002 The SPRY/B30.2-domain protein Gustavus (GUS) directly interacts with a segment in the N-terminal region of Drosophila Vasa. A gus mutation blocks posterior localization of Vasa in the oocyte, as does deletion of the GUS-binding segment of Vasa, demonstrating that GUS is required for proper subcellular localization of Vasa. Genetic screen, protein interaction assay, in vivo localization studies (loss-of-function) Developmental Cell High 12479811
2010 Arginine residues in Vasa (mouse, Xenopus, and Drosophila) are symmetrically and asymmetrically dimethylated; dPRMT5 is required for symmetrical dimethylarginine (sDMA) modification of Vasa in Drosophila. Mouse Vasa homolog (MVH/DDX4) associates with Tudor domain-containing proteins Tdrd1 and Tdrd6, and Piwi proteins Mili and Miwi, via these arginine methylation marks. Mass spectrometry (identification of dimethylarginine), co-immunoprecipitation, genetic epistasis (dPRMT5 mutants) Journal of Biological Chemistry High 20080973
2010 Drosophila Vasa has a translation-independent function in regulating mitotic chromosome condensation in germline cells. During mitosis, Vasa specifically associates (Co-IP) with condensin I components Barren (Barr) and CAP-D2 but not with the condensin II component CAP-D3, and facilitates their chromosomal localization. This mitotic function requires formation of perichromosomal Vasa bodies, which depends on piRNA pathway components Aubergine and Spindle-E. Co-immunoprecipitation, loss-of-function genetics, immunofluorescence localization during mitosis Current Biology High 21185189
2004 Drosophila Vasa RNA helicase is involved in retrotransposon silencing in the female germline; vasa mutations (along with aubergine and spindle-E mutations) cause accumulation of I-element and Het-A retrotransposon transcripts in developing oocytes. Vasa and Aubergine proteins are components of the same perinuclear ribonucleoprotein particles, and spindle-E mutation disrupts protein content of these particles. Genetic loss-of-function (mutant alleles), RT-PCR/Northern blotting for retrotransposon transcripts, immunolocalization of complex components RNA Biology Medium 17194939
1998 Drosophila Vasa is required for translational activation of gurken mRNA: vasa-null oocytes fail to accumulate GRK protein despite retaining gurken mRNA, and Vasa is required for both translation of gurken during early oogenesis and achieving wild-type gurken mRNA levels. Genetic analysis showed Vasa is also required for accumulation of other localized mRNAs (bicaudal-D, orb, oskar, nanos). Null allele analysis (genetics), in situ hybridization, immunostaining, mRNA localization assays Development High 9521895 9521910
1998 Vasa RNA helicase function is required for proper localization of gurken mRNA in the Drosophila oocyte. In vasa hypomorphic mutants, grk mRNA fails to localize correctly and GRK protein is barely detectable. Epistasis analysis with fs(1)K10 demonstrated that adequate GRK protein can accumulate in the absence of vasa if grk mRNA mislocalization is induced, suggesting Vasa acts through controlling mRNA localization. EMS mutagenesis, genetic epistasis, mRNA in situ hybridization, immunostaining Developmental Biology Medium 9676188
2015 In vivo mapping in Drosophila identified novel functional domains at the N- and C-terminal regions of Vasa (including the most C-terminal 7 amino acids, unique to Vasa orthologs) essential for posterior localization, transposon repression, embryonic patterning, and pole cell specification. Many DEAD-box helicase catalytic mutations did not prevent nuage/posterior localization or oogenesis support, indicating Vasa uses distinct domains for different cellular roles. Transgenic GFP-fusion proteins with domain deletions and point mutations, in vivo functional complementation assays in Drosophila Biology Open High 25795910
2010 In sea urchin, the SPRY/B30.2-domain protein Gustavus binds the N-terminal and DEAD-box portions of Vasa independently (in vitro binding analyses). Morpholino knockdown of Gustavus reduces Vasa protein abundance and its selective enrichment in small micromeres; overexpression of the Vasa-interacting domain of Gustavus causes Vasa to accumulate throughout the embryo, demonstrating a conserved positive regulatory role for Gustavus in post-translational control of Vasa accumulation. In vitro binding assays, morpholino knockdown, overexpression, immunofluorescence Developmental Biology High 21035437
2011 In sea urchin embryos, Vasa protein oscillates with the cell cycle, associates with the mitotic spindle and separating sister chromatids at metaphase, and is required for proper chromosome segregation and cyclinB mRNA translation. CDK activity is required for proper Vasa localization, and inhibition of Vasa synthesis arrests cells at M-phase, demonstrating a conserved cell-cycle function independent of germline determination. Morpholino knockdown, immunofluorescence (spindle localization), cell cycle analysis, cyclinB translation assay Development High 21525076
2019 In C. elegans, GLH-1/Vasa helicase activity (ATPase function) is required for its association with P granules; CRISPR-generated catalytic mutations cause loss of P-granule localization. The glycine-rich N-terminal repeats of GLH proteins promote P-granule wetting-like interactions at the nuclear periphery. Mass spectrometry identified association of GLH-1 with piRNA amplification complex components and with PCI complexes (proteasome lid, COP9, eIF3), suggesting P granules compartmentalize the cytoplasm to exclude large protein assemblies. CRISPR/Cas9 endogenous mutagenesis (28 alleles), mass spectrometry, live imaging (P-granule localization) Genetics High 31506335
2022 In C. elegans, GLH proteins (Vasa homologs) compete with each other to control Argonaute pathway specificity; the ATPase cycle of GLH-1 regulates its direct binding to the Argonaute WAGO-1, and GLH proteins bind directly to Argonaute target mRNAs, promoting amplification of small RNAs required for transgenerational inheritance. Co-immunoprecipitation, RNA-seq, genetic epistasis with ATPase-dead mutants Cell Reports High 36070689
2021 In C. elegans, novel LOTUS-domain proteins MIP-1 and MIP-2 bind and anchor the Vasa homolog GLH-1 within P granules; they are jointly required for coalescence of MEG-3, GLH-1, and PGL proteins. MIP-1/2 contain LOTUS domains and IDRs, form homo- and heterodimers, and serve as scaffolds for RNP networks that recruit Vasa to germ granules. Co-immunoprecipitation, CRISPR knockouts, live imaging, protein interaction mapping eLife High 34223818
2012 Overexpression of VASA (DDX4) and/or DAZL in human embryonic stem cells and iPSCs promotes their differentiation to primordial germ cells and enhances meiotic progression in vitro, demonstrating that VASA protein expression is sufficient to drive meiotic maturation of human-derived germ cells. Overexpression in hESCs/iPSCs, immunofluorescence for meiotic markers, flow cytometry Stem Cells Medium 22162380
2023 In Bombyx mori, BmPrmt5 (type II arginine methyltransferase) dimethylates Vasa at residues R35, R54, and R56 as identified by mass spectrometry; CRISPR loss-of-function of either BmPrmt5 or BmVasa produces nearly identical male and female sterility with severe sperm morphology defects, establishing a BmPrmt5-Vasa regulatory module essential for spermatogenesis. CRISPR/Cas9 knockout, mass spectrometry (dimethylarginine identification), RNA-seq, immunofluorescence PLoS Genetics High 36634107
2000 Human VASA (DDX4) protein is localized to the cytoplasm of germ cells, including migratory primordial germ cells, and is expressed specifically in ovary and testis with no detectable expression in somatic tissues, as established by Northern analysis and immunohistochemistry with polyclonal antibodies on fixed tissues. Northern blot (tissue panel), immunohistochemistry in fetal and adult tissue PNAS Medium 10920202
2010 Mouse Vasa homolog (MVH/DDX4) protein is localized in nuage structures of spermatogenic cells including intermitochondrial cement (IMC), loose aggregates, and chromatoid bodies (CBs) at distinct stages of spermatogenesis, as determined by immunofluorescence and immunoelectron microscopy. The protein transitions through these nuage compartments in a stage-dependent manner. Immunofluorescence microscopy and nanogold immunoelectron microscopy with anti-MVH antibody Histochemistry and Cell Biology Medium 20401665

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Structural basis for RNA unwinding by the DEAD-box protein Drosophila Vasa. Cell 476 16630817
2000 The human VASA gene is specifically expressed in the germ cell lineage. Proceedings of the National Academy of Sciences of the United States of America 465 10920202
1990 Posterior localization of vasa protein correlates with, but is not sufficient for, pole cell development. Genes & development 345 2384213
2000 Isolation of chicken vasa homolog gene and tracing the origin of primordial germ cells. Development (Cambridge, England) 308 10821771
2000 The function and regulation of vasa-like genes in germ-cell development. Genome biology 264 11178242
1998 vasa is required for GURKEN accumulation in the oocyte, and is involved in oocyte differentiation and germline cyst development. Development (Cambridge, England) 259 9521895
1999 Expression of vasa(vas)-related genes in germline cells and totipotent somatic stem cells of planarians. Developmental biology 224 9918696
2014 RNA clamping by Vasa assembles a piRNA amplifier complex on transposon transcripts. Cell 205 24910301
1997 A vasa-like gene in zebrafish identifies putative primordial germ cells. Mechanisms of development 205 9376327
2007 The dynamic vasa vasorum. Cardiovascular research 184 17631284
1996 Oskar protein interaction with Vasa represents an essential step in polar granule assembly. Genes & development 179 8804312
2000 The vasa-like gene, olvas, identifies the migration path of primordial germ cells during embryonic body formation stage in the medaka, Oryzias latipes. Development, growth & differentiation 174 10969731
2001 Universal occurrence of the vasa-related genes among metazoans and their germline expression in Hydra. Development genes and evolution 163 11466525
1998 Oocyte polarity depends on regulation of gurken by Vasa. Development (Cambridge, England) 163 9521910
2022 High-throughput total RNA sequencing in single cells using VASA-seq. Nature biotechnology 161 35760914
2001 Vasa homolog genes in mammalian germ cell development. Cell structure and function 154 11565805
1995 Aquaporin-1 water channels in short and long loop descending thin limbs and in descending vasa recta in rat kidney. The American journal of physiology 151 7541952
2010 Contrast-enhanced ultrasound imaging of the vasa vasorum: from early atherosclerosis to the identification of unstable plaques. JACC. Cardiovascular imaging 137 20633855
1999 Characterization of zebrafish primordial germ cells: morphology and early distribution of vasa RNA. Developmental dynamics : an official publication of the American Association of Anatomists 137 10536055
2007 Vasa unveils a common origin of germ cells and of somatic stem cells from the posterior growth zone in the polychaete Platynereis dumerilii. Developmental biology 134 17467683
2012 Divergent RNA-binding proteins, DAZL and VASA, induce meiotic progression in human germ cells derived in vitro. Stem cells (Dayton, Ohio) 131 22162380
2010 Vasa genes: emerging roles in the germ line and in multipotent cells. BioEssays : news and reviews in molecular, cellular and developmental biology 131 20586054
2014 Zebrafish vasa is required for germ-cell differentiation and maintenance. Molecular reproduction and development 113 25257909
2000 Neutrophil and endothelial cell activation in the vasa vasorum in vasculo-Behçet disease. Histopathology 110 10759951
2013 The DEAD-box helicase Vasa: evidence for a multiplicity of functions in RNA processes and developmental biology. Biochimica et biophysica acta 104 23587717
2015 Vasa vasorum in atherosclerosis and clinical significance. International journal of molecular sciences 102 26006236
2004 The RNA interference proteins and vasa locus are involved in the silencing of retrotransposons in the female germline of Drosophila melanogaster. RNA biology 102 17194939
2001 Anti-B7-1 blocks mononuclear cell adherence in vasa recta after ischemia. Kidney international 102 11576355
2009 In vivo RNA interference in oyster--vasa silencing inhibits germ cell development. The FEBS journal 83 19476495
1994 Transport of sodium and urea in outer medullary descending vasa recta. The Journal of clinical investigation 80 8282790
2002 Identification of a transcriptional regulatory region for germline-specific expression of vasa gene in Drosophila melanogaster. Mechanisms of development 79 11850184
2009 The vasa regulatory region mediates germline expression and maternal transmission of proteins in the malaria mosquito Anopheles gambiae: a versatile tool for genetic control strategies. BMC molecular biology 78 19573226
2015 The Crystal Structure of the Drosophila Germline Inducer Oskar Identifies Two Domains with Distinct Vasa Helicase- and RNA-Binding Activities. Cell reports 73 26190108
2006 Pulmonary artery adventitial fibroblasts cooperate with vasa vasorum endothelial cells to regulate vasa vasorum neovascularization: a process mediated by hypoxia and endothelin-1. The American journal of pathology 72 16723696
2004 The oyster vasa-like gene: a specific marker of the germline in Crassostrea gigas. Biochemical and biophysical research communications 72 14985097
2010 Arginine methylation of vasa protein is conserved across phyla. The Journal of biological chemistry 71 20080973
2002 VASA localization requires the SPRY-domain and SOCS-box containing protein, GUSTAVUS. Developmental cell 67 12479811
2017 The LOTUS domain is a conserved DEAD-box RNA helicase regulator essential for the recruitment of Vasa to the germ plasm and nuage. Genes & development 66 28536148
2002 Two isoforms of vasa homologs in a teleost fish: their differential expression during germ cell differentiation. Mechanisms of development 65 11804791
2008 Vasa and nanos are coexpressed in somatic and germ line tissue from early embryonic cleavage stages through adulthood in the polychaete Capitella sp. I. Development genes and evolution 63 18651171
2010 A role for vasa in regulating mitotic chromosome condensation in Drosophila. Current biology : CB 59 21185189
2012 Small-vessel vasculitis surrounding an uninflamed temporal artery and isolated vasa vasorum vasculitis of the temporal artery: two subsets of giant cell arteritis. Arthritis and rheumatism 58 21953306
2013 Identification and migration of primordial germ cells in Atlantic salmon, Salmo salar: characterization of vasa, dead end, and lymphocyte antigen 75 genes. Molecular reproduction and development 57 23239145
2018 Medial Hypoxia and Adventitial Vasa Vasorum Remodeling in Human Ascending Aortic Aneurysm. Frontiers in cardiovascular medicine 55 30276199
1999 Isolation and characterization of a Bombyx vasa-like gene. Development genes and evolution 54 11252184
2011 DDX4 (VASA) is conserved in germ cell development in marsupials and monotremes. Biology of reproduction 53 21653890
2010 Post-translational regulation by gustavus contributes to selective Vasa protein accumulation in multipotent cells during embryogenesis. Developmental biology 53 21035437
2011 The DEAD-box RNA helicase Vasa functions in embryonic mitotic progression in the sea urchin. Development (Cambridge, England) 49 21525076
2002 Germ line development in the grasshopper Schistocerca gregaria: vasa as a marker. Developmental biology 49 12453463
2008 Germ cells in the crustacean Parhyale hawaiensis depend on Vasa protein for their maintenance but not for their formation. Developmental biology 48 19013453
1993 Comparative cryopreservation and capacitation of spermatozoa from epididymides and vasa deferentia of the domestic cat. Journal of reproduction and fertility. Supplement 48 8229940
2014 Use of DEAD-box polypeptide-4 (Ddx4) gene promoter-driven fluorescent reporter mice to identify mitotically active germ cells in post-natal mouse ovaries. Molecular human reproduction 47 25147160
2011 The multiple hats of Vasa: its functions in the germline and in cell cycle progression. Molecular reproduction and development 46 21823188
2014 Role of the vasa vasorum and vascular resident stem cells in atherosclerosis. BioMed research international 45 24724094
2016 Glycolysis and oxidative phosphorylation are essential for purinergic receptor-mediated angiogenic responses in vasa vasorum endothelial cells. American journal of physiology. Cell physiology 44 27856430
2006 Germ-plasm specification and germline development in the parthenogenetic pea aphid Acyrthosiphon pisum: Vasa and Nanos as markers. The International journal of developmental biology 44 16525937
2010 Localization of mouse vasa homolog protein in chromatoid body and related nuage structures of mammalian spermatogenic cells during spermatogenesis. Histochemistry and cell biology 43 20401665
2019 Germline Maintenance Through the Multifaceted Activities of GLH/Vasa in Caenorhabditis elegans P Granules. Genetics 42 31506335
2016 FACS-sorted putative oogonial stem cells from the ovary are neither DDX4-positive nor germ cells. Scientific reports 42 27301892
2015 Essential elements for translation: the germline factor Vasa functions broadly in somatic cells. Development (Cambridge, England) 42 25977366
2020 Adventitial fibroblast-derived vascular endothelial growth factor promotes vasa vasorum-associated neointima formation and macrophage recruitment. Cardiovascular research 39 31241138
2008 Zebrafish primordial germ cell cultures derived from vasa::RFP transgenic embryos. Stem cells and development 39 18576915
1998 Requirement for the vasa RNA helicase in gurken mRNA localization. Developmental biology 39 9676188
2015 Angiogenesis Inhibitor, Endostar, Prevents Vasa Vasorum Neovascularization in a Swine Atherosclerosis Model. Journal of atherosclerosis and thrombosis 38 26016418
2015 VASA (DDX4) is a Putative Marker for Spermatogonia, Spermatocytes and Round Spermatids in Stallions. Reproduction in domestic animals = Zuchthygiene 37 26482643
2017 Classification and Functional Characterization of Vasa Vasorum-Associated Perivascular Progenitor Cells in Human Aorta. Stem cell reports 34 28552602
2014 Vasa identifies germ cells and critical stages of oogenesis in the Asian seabass. International journal of biological sciences 31 24550690
2021 Building RNA-protein germ granules: insights from the multifaceted functions of DEAD-box helicase Vasa/Ddx4 in germline development. Cellular and molecular life sciences : CMLS 29 34921622
2014 The Vasa Homolog RDE-12 engages target mRNA and multiple argonaute proteins to promote RNAi in C. elegans. Current biology : CB 29 24684931
2004 Expression of TRPC4 channel protein that interacts with NHERF-2 in rat descending vasa recta. American journal of physiology. Cell physiology 29 15590898
1999 Endothelin alters the reactivity of vasa vasorum: mechanisms and implications for conduit vessel physiology and pathophysiology. British journal of pharmacology 29 10578136
1990 Resistance of descending vasa recta to the transport of water. The American journal of physiology 29 1699435
2018 Local adventitial anti-angiogenic gene therapy reduces growth of vasa-vasorum and in-stent restenosis in WHHL rabbits. Journal of molecular and cellular cardiology 28 30003882
2013 Adenosine A1 receptors promote vasa vasorum endothelial cell barrier integrity via Gi and Akt-dependent actin cytoskeleton remodeling. PloS one 28 23613714
2005 KATP channel conductance of descending vasa recta pericytes. American journal of physiology. Renal physiology 28 16048905
2017 Stage-specific expression of DDX4 and c-kit at different developmental stages of the porcine testis. Animal reproduction science 27 29338902
2016 An unregulated regulator: Vasa expression in the development of somatic cells and in tumorigenesis. Developmental biology 27 27179696
2014 DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers. Biochemical and biophysical research communications 27 24727449
2013 Splice variants and promoter methylation status of the Bovine Vasa Homology (Bvh) gene may be involved in bull spermatogenesis. BMC genetics 27 23815438
2002 Ca(2+) signaling and membrane potential in descending vasa recta pericytes and endothelia. American journal of physiology. Renal physiology 27 12217877
2015 In vivo mapping of the functional regions of the DEAD-box helicase Vasa. Biology open 25 25795910
2012 Vasa-Like DEAD-Box RNA Helicases of Schistosoma mansoni. PLoS neglected tropical diseases 25 22720105
1999 On the regulation of tone in vasa vasorum. Cardiovascular research 25 10325971
2021 Novel LOTUS-domain proteins are organizational hubs that recruit C. elegans Vasa to germ granules. eLife 23 34223818
2013 Cloning, expression promoter analysis of vasa gene in Japanese flounder (Paralichthys olivaceus). Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 22 23796850
2012 Germ cell specific expression of Vasa in rare minnow, Gobiocypris rarus. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 22 22357168
2021 Pericyte-specific deletion of ninjurin-1 induces fragile vasa vasorum formation and enhances intimal hyperplasia of injured vasculature. American journal of physiology. Heart and circulatory physiology 21 33961504
2019 Germ Cell Lineage Homeostasis in Drosophila Requires the Vasa RNA Helicase. Genetics 21 31484689
2018 Expression of vasa, piwi, and nanos during gametogenesis in Typosyllis antoni (Annelida, Syllidae). Evolution & development 21 30094969
2016 Expression Pattern of Mouse Vasa Homologue (MVH) in the Ovaries of C57BL/6 Female Mice. Medical science monitor : international medical journal of experimental and clinical research 21 27460133
2014 Atherosclerosis and atheroma plaque rupture: normal anatomy of vasa vasorum and their role associated with atherosclerosis. TheScientificWorldJournal 21 24790560
2023 The Prmt5-Vasa module is essential for spermatogenesis in Bombyx mori. PLoS genetics 20 36634107
2022 A family of C. elegans VASA homologs control Argonaute pathway specificity and promote transgenerational silencing. Cell reports 20 36070689
2014 Piwi regulates Vasa accumulation during embryogenesis in the sea urchin. Developmental dynamics : an official publication of the American Association of Anatomists 20 24218044
2014 Light and electron microscopic analyses of Vasa expression in adult germ cells of the fish medaka. Gene 20 24814190
2012 Characterization of the vasa gene in the Chinese mitten crab Eriocheir sinensis: a germ line molecular marker. Journal of insect physiology 20 22562064
2012 Nestin and WT1 expression in small-sized vasa vasorum from human normal arteries. Histology and histopathology 20 22806906
2009 An evolutionary transition of Vasa regulation in echinoderms. Evolution & development 20 19754712
2007 A vasa-like gene in the giant freshwater prawn, Macrobrachium rosenbergii. Molecular reproduction and development 20 17186538
2017 Multiple Functions of the DEAD-Box Helicase Vasa in Drosophila Oogenesis. Results and problems in cell differentiation 19 28779316