miwi, a Murine Homolog of piwi, Encodes a Cytoplasmic Protein Essential for Spermatogenesis
Developmental CellPublished 1 June 2002Open access
Wei Deng, Haifan Lin
Citations878
SJR quartileQ1
SJR score5.18
SNIP2.05
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The cloning of a murine piwi gene (miwi) essential for spermatogenesis is reported, and MIWI complexes with mRNAs of ACT and CREM target genes are reported, suggesting that MIWI may control spermiogenesis by regulating the stability of these m RNAs.
Abstract
The piwi family genes are crucial for stem cell self-renewal, RNA silencing, and translational regulation in diverse organisms. However, their function in mammals remains unexplored. Here we report the cloning of a murine piwi gene (miwi) essential for spermatogenesis. miwi encodes a cytoplasmic protein specifically expressed in spermatocytes and spermatids. miwi(null) mice display spermatogenic arrest at the beginning of the round spermatid stage, resembling the phenotype of CREM, a master regulator of spermiogenesis. Furthermore, mRNAs of ACT (activator of CREM in testis) and CREM target genes are downregulated in miwi(null) testes. Whereas MIWI and CREM do not regulate each other's expression, MIWI complexes with mRNAs of ACT and CREM target genes. Hence, MIWI may control spermiogenesis by regulating the stability of these mRNAs.
Keywords
Agricultural and Biological SciencesBiochemistry, Genetics and Molecular Biology
Biomedicine & PharmacotherapyAntibodies, a laboratory manual
12,466 Citations1989
A second edition of Antibodies: A Laboratory Manual is being published in September 2013, Revised, extended and updated by Edward Greenfield of the Dana-Farber Cancer Center, the material has been recast with extensive new information and new chapters have been added.
Manipulating the mouse embryo: A laboratory manual
4,473 Citations1986Brigid Hogan, Frank Costantini +1 more
Here are recorded the tech- niques for preparing, inserting and analysing DNA sequences, for retroviral infection of mice, for production and use of EC and EK cells as vehicles for engineered sequences and for nuclear transplantation - all against a background of the basic procedures required for pro- ducing and handling the em- bryos.
NatureFailure of blood-island formation and vasculogenesis in Flk-1-deficient mice
3,947 Citations1995Fouad Shalaby, Janet Rossant +5 more
The generation of mice deficient in Flk-1 by disruption of the gene using homologous recombination in embryonic stem (ES) cells is reported, indicating that FlK-1 is essential for yolk-sac blood-island formation and vasculogenesis in the mouse embryo.
ScienceCheckpoints: Controls That Ensure the Order of Cell Cycle Events
3,029 Citations1989Leland H. Hartwell, Ted Weinert
It appears that some checkpoints are eliminated during the early embryonic development of some organisms; this fact may pose special problems for the fidelity of embryonic cell division.
CellThe rde-1 Gene, RNA Interference, and Transposon Silencing in C. elegans
1,308 Citations1999Hiroaki Tabara, Madathia Sarkissian +6 more
It is shown that rde-1 is a member of the piwi/sting/argonaute/zwille/eIF2C gene family conserved from plants to vertebrates and the possibility that one natural function of RNAi is transposon silencing is discussed.
Genes & DevelopmentA novel class of evolutionarily conserved genes defined by <i>piwi</i> are essential for stem cell self-renewal
982 Citations1998Daniel N. Cox, Anna Chao +4 more
The Drosophila piwi gene is cloned and characterized and it is shown that it is required for the asymmetric division of GSCs to produce and maintain a daughter GSC but is not essential for the further differentiation of the committed daughter cell.
Seminars in Cell and Developmental BiologyThe central role of Sertoli cells in spermatogenesis
856 Citations1998Michael D. Griswold
Sertoli cells are the somatic cells of the testis that are essential for testis formation and spermatogenesis and the action of FSH minimally serves to promote sperMatogenic output by increasing the number of SERToli cells.
DevelopmentA novel group of <i>pumilio</i> mutations affects the asymmetric division of germline stem cells in the <i>Drosophila</i> ovary
701 Citations1997Haifan Lin, Allan C. Spradling
The self-renewing asymmetric division of germline stem cells in the Drosophila ovarian germline, as marked by the spectrosome, a cytoplasmic structure rich in membrane skeletal proteins that marks the lineage of germ line stem cells is described.
Celldecapentaplegic Is Essential for the Maintenance and Division of Germline Stem Cells in the Drosophila Ovary
678 Citations1998Ting Xie, Allan C. Spradling
It is shown that the BMP2/4 homolog decapentaplegic (dpp) is specifically required to maintain female germline stem cells and promote their division and helps define a niche that controls germlinestem cell proliferation.
The EMBO JournalAGO1 defines a novel locus of Arabidopsis controlling leaf development
678 Citations1998Karen Bohmert, Isabelle Camus +4 more
An allelic series of the novel argonaute mutant (ago1‐1 to ago1‐6) of the herbaceous plant Arabidopsis thaliana has been isolated and encodes a putative 115 kDa protein with sequence similarity to translation products of a novel gene family present in nematodes as well as humans.
NatureThe mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis
638 Citations1997Matteo Ruggiu, R.M. Speed +6 more
Dazla protein is cytoplasmic in male and female germ cells, unlike the nuclear RBM protein, demonstrating that Dazla is essential for the differentiation of germ cells.
Genes & DevelopmentThe mouse homolog of <i>Drosophila Vasa</i> is required for the development of male germ cells
623 Citations2000Satomi Tanaka, Yayoi Toyooka +6 more
It is demonstrated that male mice homozygous for a targeted mutation of Mvh exhibit a reproductive deficiency, which causes a deficiency in the proliferation and differentiation of mouse male germ cells.
DevelopmentRole of <i>c-kit</i> in mouse spermatogenesis: identification of spermatogonia as a specific site of <i>c-kit</i> expression and function
617 Citations1991Kazuya Yoshinaga, Satomi Nishikawa +5 more
It is indicated that the survival and/or proliferation of the differentiating type A spermatogonia requires c-kit, but the primitive (undifferentiated) type C sperMatogonia or sPermatogenic stem cells are independent from c-Kit.
NatureSpermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice
593 Citations1996F. Nantel, Lucia Monaco +7 more
It is shown that CREM deficiency results in the lack of postmeiotic cell-specific gene expression, and the complete lack of spermatozoa in the mutant mice is reminiscent of cases of human infertility.
Proceedings of the National Academy of SciencesTargeted gene disruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility.
559 Citations1996David J. Dix, James W. Allen +6 more
Analysis of nuclei and genomic DNA indicated that the failure of meiosis in Hsp70-2 -/- mice was coincident with a dramatic increase in spermatocyte apoptosis, suggesting that HSP 70-2 participates in synaptonemal complex function during meiosis during male germ cells and is linked to mechanisms that inhibit apoptosis.
Development<i>piwi</i> encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells
556 Citations2000Daniel N. Cox, Anna Chao +1 more
It is shown that piwi encodes a novel nucleoplasmic protein present in both somatic and germline cells, with the highly conserved C-terminal region essential for its function.
NatureSevere impairment of permatogenesis in mice lacking the CREM gene
522 Citations1996Julie A. Blendy, Klaus H. Kaestner +3 more
The findings indicate that the CREM gene is essential for spermatogenesis, and mice deficient for this transcription factor could serve as a model system for the study of idiopathic infertility in men.
Nature GeneticsGlobozoospermia in mice lacking the casein kinase II α′ catalytic subunit
437 Citations1999Xin Xu, Paul Toselli +2 more
It is found here that Csnk2a2 is preferentially expressed in late stages of spermatogenesis, and male mice in which C Snk 2a2 has been disrupted are infertile, with oligospermia and globozoospermia ('round-headed' spermatozoa), the first demonstration of a unique role for a Ck2 isoform in development.
Trends in Biochemical SciencesDomains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain
426 Citations2000Lorenzo Cerutti, Nina Mian +1 more
Genes & Developmentbag-of-marbles: a Drosophila gene required to initiate both male and female gametogenesis.
423 Citations1990Dennis McKearin, Allan C. Spradling
This work identified and characterized a gene, bag-of-marbles (bam), that disrupts cyst formation in both sexes and suggested it might be involved in the specific cell-cycle alterations that occur during cystocyte divisions.
NatureMeiotic cell cycle requirement for a fly homologue of human Deleted in Azoospermia
404 Citations1996Charles G. Eberhart, Jean Z. Maines +1 more
The cloning and characterization of the Drosophila gene boule is described, which is a homologue of DAZ, and it is indicated that Boule and DAZ have an essential meiotic function in fly and human spermatogenesis.
CellInactivation of the HR6B Ubiquitin-Conjugating DNA Repair Enzyme in Mice Causes Male Sterility Associated with Chromatin Modification
397 Citations1996Henk P. Roest, J van Klaveren +11 more
The phenotype of the first animal mutant in the ubiquitin pathway is reported: inactivation of the hHR6B-homologous gene in mice causes male infertility, and this findings provide a parallel between yeast sporulation and mammalian spermatogenesis and strongly implicate h HR6-dependent ubiquitination in chromatin remodeling.
Proceedings of the National Academy of SciencesIdentifying mRNA subsets in messenger ribonucleoprotein complexes by using cDNA arrays
395 Citations2000Scott A. Tenenbaum, Craig C. Carson +2 more
The use of cDNA arrays to identify subsets of mRNAs contained in endogenous messenger ribonucleoprotein complexes (mRNPs) that are cell type specific is described and it is suggested that the association of structurally related m RNAs into mRNP complexes is dynamic and may help regulate posttranscriptional events such as mRNA turnover and translation.
The EMBO JournalRole of the ZWILLE gene in the regulation of central shoot meristem cell fate during Arabidopsis embryogenesis
377 Citations1998Bernard Moussian, Heiko Schoof +3 more
It is proposed that ZLL relays positional information required to maintain stem cells of the developing shoot meristem in an undifferentiated state during the transition from embryonic development to repetitive postembryonic organ formation.
Nature GeneticsCyclin A1 is required for meiosis in the male mouse
374 Citations1998Dong Liu, Martin M. Matzuk +4 more
Meiosis arrest in Ccna1–/– males was associated with increased germ cell apoptosis, desynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase, indicating cyclin A1 is essential for spermatocyte passage into the first meiotic division in male mice, a function that cannot be complemented by the concurrently expressed B-type cyclins.
Development<i>aubergine</i>encodes a<i>Drosophila</i>polar granule component required for pole cell formation and related to eIF2C
327 Citations2001Adam N. Harris, Paul M. Macdonald
It is found that Aubergine protein is related to eukaryotic translation initiation factor 2C and is itself a polar granule component, suggesting that the roles of these proteins diverge during embryogenesis.
Proceedings of the National Academy of SciencesAbnormal spermatogenesis and reduced fertility in transition nuclear protein 1-deficient mice
320 Citations2000Yaqing Yu, Yun Zhang +7 more
It is concluded that TP1 is not essential for histone displacement or chromatin condensation, and the absence of TP1 may partially be compensated for by TP2 and P2 precursor, but this dysregulation of nucleoprotein replacement results in an abnormal pattern of chromatin Condensation and in reduced fertility.
Genes & DevelopmentThe gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse.
274 Citations1996Guojie Zhao, Ke‐Yu Deng +3 more
This study provides the first genetic evidence that a murine germ cell-produced factor, BMP8B, is required for the resumption of male germ-cell proliferation in early puberty, and for germ- cell survival and fertility in the adult.
Mechanisms of DevelopmentTwo mouse piwi-related genes: miwi and mili
271 Citations2001Satomi Kuramochi‐Miyagawa, Tohru Kimura +7 more
The deduced amino acid sequences of mouse homologues MIWI and MILI showed that each contains a well-conserved C-terminal PIWI domain and that each shares significant homology with PIWI and their human counterparts HIWI.
DevelopmentRegulation of proliferation and differentiation in spermatogonial stem cells: the role of c-kit and its ligand SCF
248 Citations2000Hiroshi Ohta, Kentaro Yomogida +2 more
It is demonstrated that donor germ cells transplanted into seminiferous tubules of mutant mice with male sterility contained spermatogonial stem cells and that stimulation of c-kit receptor by its ligand was necessary for maintenance of differentiated type A sperMatogonia but not for proliferation of undifferentiated type A
NatureGene silencing in worms and fungi
246 Citations2000Caterina Catalanotto, Gianluca Azzalin +2 more
It is shown that two distantly related organisms, the nematode Caenorhabditis elegans and the fungus Neurospora crassa, both use a similar protein to control the process of gene silencing, suggesting that they may share an ancestral mechanism that evolved to protect the genome against invasion by foreign DNA.
DevelopmentMouse primordial germ cells lacking β1 integrins enter the germline but fail to migrate normally to the gonads
243 Citations1999Robert Anderson, Reinhard Fässler +7 more
A role for beta1-containing integrins in the development of the germline is demonstrated, although an equivalent role for * integrin subunit(s) has yet to be established.
NatureArrest of spermatogenesis and defective breast development in mice lacking A-myb
227 Citations1997A Toscani, Richard V. Mettus +6 more
It is reported here that mice homozygous for a germline mutation in A-myb develop to term but show defects in growth after birth and male infertility due to a block in spermatogenesis.
Seminars in Cell and Developmental BiologyGenetic control of cell proliferation and differentiation inDrosophilaspermatogenesis
224 Citations1998Margaret T. Fuller
Outlines of the genetic circuitry regulating male gametogenesis in Drosophila have begun to appear and a cross-regulatory mechanism might act to delay the G2/M transition of meiosis I until genes required for spermatid differentiation have been transcribed.
NatureCBP-independent activation of CREM and CREB by the LIM-only protein ACT
223 Citations1999Gian María Fimia, Dario De Cesare +1 more
A testis-derived complementary DNA encoding a protein that is termed ACT (for activator of CREM in testis), a LIM-only protein which specifically associates with CREM, which strongly stimulates CREM transcriptional activity in yeast and mammalian cells and contains an intrinsic activation function.
Celltwine, a cdc25 homolog that functions in the male and female germline of drosophila
207 Citations1992Luke Alphey, Juan Jiménez +4 more
Analysis of a twine mutant suggests a requirement for the gene during oogenesis, during syncytial embryonic development, and for male meiosis, which does not occur in homozygous twine males.
Molecular CellLate Arrest of Spermiogenesis and Germ Cell Apoptosis in Mice Lacking the TBP-like TLF/TRF2 Gene
206 Citations2001Igor Martianov, Gian María Fimia +4 more
Metazoan genomes encode two related proteins, TBP and the TBP-like factor (TLF/TRF2), sharing a highly conserved saddle-like domain, which is not required for embryonic development in the mouse but is essential for spermiogenesis.
DevelopmentHSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes
204 Citations1997Dahai Zhu, David J. Dix +1 more
This study used immunoprecipitation-coupled western blot and in vitro reconstitution experiments to show that HSP70-2 interacts with CDC2 in the mouse testis, appears to be a molecular chaperone for CDC2, and is required forCDC2/cyclin B1 complex formation.
Seminars in Cell and Developmental BiologyRegulation of gene expression during spermatogenesis
189 Citations1998Edward M. Eddy
Spermatogenesis occurs in successive mitotic, meiotic and post-meiotic phases and genes expressed during this process encode proteins necessary for processes specific to the different phases of germ cell development, subject to transcriptional, translational andPost-translational regulation.
ScienceSpermiogenesis Deficiency in Mice Lacking the <i>Trf2</i> Gene
188 Citations2001Di Zhang, Tarja‐Leena Penttilä +3 more
It is speculated that mammals may have evolved more specialized TRF2 functions in the testis that involve transcriptional regulation of genes essential for spermiogenesis.
Development<i>aubergine</i> enhances <i>oskar</i> translation in the <i>Drosophila</i> ovary
167 Citations1996Joan Wilson, Joanne E. Connell +1 more
It is shown that aubergine is also required for posterior body patterning, as the small fraction of eggs from Aubergine- mothers that are fertilized develop into embryos which lack abdominal segmentation.
Nature GeneticsA double-stranded RNA binding protein required for activation of repressed messages in mammalian germ cells
163 Citations1999Jun Zhong, Antoine H.F.M. Peters +2 more
It was shown that failure to synthesize the protamines resulted in delayed replacement of the transition proteins and subsequent failure of spermiation, and the timing of Prbp expression suggests that it may function as a chaperone in the assembly of specific translationally regulated ribonucleoprotein particles.
GeneticsGenetic and Molecular Characterization of sting, a Gene Involved in Crystal Formation and Meiotic Drive in the Male Germ Line of Drosophila melanogaster
153 Citations1999Armin Schmidt, Gioacchino Palumbo +4 more
The sting mutation, caused by a P element inserted into polytene region 32D, was isolated by a screen for male sterile insertions in Drosophila melanogaster and was cloned and shown to code for a putative protein that is 866 amino acids long.
GeneticsThe Drosophila Cystoblast Differentiation Factor, <i>benign gonial cell neoplasm</i>, Is Related to DExH-box Proteins and Interacts Genetically With <i>bag-of-marbles</i>
134 Citations2000Benjamin Ohlstein, Christine A. Lavoie +3 more
Cl cloning and characterization of bgcn are presented and it is proposed that Bgcn and Bam may be involved in regulating translational events that are necessary for activation of the cystoblast differentiation program.
DevelopmentThe <i>Drosophila</i> cdc25 homolog <i>twine</i> is required for meiosis
133 Citations1992Catherine Courtot, Christian Fankhauser +2 more
Phenotypic analysis of mat(2)synHB5 mutant flies revealed a complete block of meiosis in males and severe meiotic defects in females, and a missense mutation in the twine gene abolished its ability to complement a mutation in Schizosaccharomyces pombe cdc25.
Annual Review of GeneticsTHE TAO OF STEM CELLS IN THE GERMLINE
118 Citations1997Haifan Lin
The establishment and self-renewing division of GSCs are controlled by extracellular signals such as hormones from the hypothalamic-pituitary axis and local interactions between G SCs and their neighboring cells.
Molecular and Cellular BiologyFunctional Compensation by <i>Egr4</i> in <i>Egr1</i>-Dependent Luteinizing Hormone Regulation and Leydig Cell Steroidogenesis
86 Citations2000Warren G. Tourtellotte, Rakesh Nagarajan +2 more
It is shown that serum LH levels in male Egr1-deficient mice are adequate for maintenance of Leydig cell steroidogenesis and fertility because of partial functional redundancy with the closely related transcription factor Egr4.
Proceedings of the National Academy of SciencescAMP-response element modulator tau is a positive regulator of testis angiotensin converting enzyme transcription.
79 Citations1996Yudong Zhou, Zuoming Sun +3 more
Competitive gel shift shows that recombinant CREM tau protein and testis nuclear proteins have a similar specificity of binding to the tests ACE CRE, and functional analysis using in vitro transcription and transfection studies demonstrate that CREMTau protein is a transcriptional activator of the testis ACE promoter.
GeneMolecular cloning and characterization of a rabbit eIF2C protein
69 Citations1998Cheng Zou, Zhongli Zhang +2 more
Biology of ReproductionHaploid Gene Expression: Temporal Onset and Storage Patterns of 13 Novel Transcripts during Rat and Mouse Spermiogenesis1
54 Citations1995Tarja‐Leena Penttilä, Li Yuan +3 more
Similarity in the stage-specific expression pattern displayed by this group of haploid-specific genes strongly suggests the presence of common regulatory mechanisms that act during spermiogenesis, and these genes also provide a means for further studies of these mechanisms.
EndocrinologyDevelopmentally Regulated Expression of Cyclin D3 and Its Potential in Vivo Interacting Proteins during Murine Gametogenesis*
51 Citations1999Qi Zhang, Xiangyuan Wang +1 more
Observations suggest unique roles for cyclin D3 in the control of cell division and differentiation in the germ line and the differential regulation of mitotic and meiotic cell cycles during male and female gametogenesis.
Molecular and Cellular EndocrinologyTranscriptional cascades during spermatogenesis: pivotal role of CREM and ACT
48 Citations2001Gian María Fimia, Aurore Morlon +3 more
Using homologous recombination, CREM-mutant mice are generated that display a complete block at the first step of spermiogenesis and ACT (Activator of CREM in Testis), a testis-specific coactivator constituted by a repeat of four and half LIM domains, is presented.
GenomicsHuman Eukaryotic Initiation Factor EIF2C1 Gene: cDNA Sequence, Genomic Organization, Localization to Chromosomal Bands 1p34–p35, and Expression
47 Citations1999Robert Koesters, Volker Adams +10 more
The cloning and characterization of the human eukaryotic protein translation initiation factor EIF2C1 gene suggest that human EIF1 might play an important physiological role.
Novartis Foundation symposiumAxis Determination in Insect Embryos
42 Citations2007Christiane Nüsslein‐Volhard, Siegfried Roth
These studies suggest the following model: for the anteroposterior axis of the embryo, three groups of maternal genes define three largely independent systems that determine (1) the anterior segmented region of head and thorax, (2) the posterior segmenting region of the abdomen, and (3) the terminal non-segmented regions of acron and telson.
Molecular Reproduction and DevelopmentCREM: A master-switch regulating the balance between differentiation and apoptosis in male germ cells
40 Citations2000Paolo Sassone‐Corsi
Cyclic AMP‐responsive element modulator (CREM) is a transcription factor highly expressed in the post‐meiotic germ cells of the testis that needs a tissue‐specific co‐activator, ACT (activator of CREM in testis) to elicit its regulatory function inTestis.
Biology of ReproductionRapid cDNA Sequencing in Combination with RNA Expression Studies in Mice Identifies a Large Number of Male Germ Cell-Specific Sequence Tags1
39 Citations1995Li Yuan, Jianguo Liu +1 more
Developmental BiologyThe MouseTsxGene Is Expressed in Sertoli Cells of the Adult Testis and Transiently in Premeiotic Germ Cells during Puberty
34 Citations1998David B. Cunningham, Dominique Segretain +3 more
Tsx is the first gene to show a pattern of germ cell expression that is apparently specific to the pubertal testis and supports the hypothesis that during the first wave of normal spermatogenesis, the advent of a late-stage cell type is responsible for extinguishing expression in sperMatogonia in normal adult testis.
Journal of Biological ChemistryStructure and organization of mouse U3B RNA functional genes.
34 Citations1988Sylvie Mazan, Jean‐Pierre Bachellerie
This small multigene family of mouse U3B genes appears to have undergone a concerted evolution in rodents, suggesting the functional importance of sequences well upstream from the distal sequence element of the promoter.
International Journal of AndrologyCharacterization and expression of a stage specific antigen by monoclonal antibody TRA 54 in testicular germ cells
23 Citations1998PEREIRA, Tanaka +7 more
The expression of these antigens during testicular germ cell development should be of interest in relation to the biogenesis of organelles such as the chromatoid body and acrosome and will be a useful stage-specific molecular marker for the study of spermatogenesis.