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| Open AccessCEP128 is involved in spermatogenesis in humans and mice
CEP128 is a centrosomal protein important for the organization of centriolar microtubules. Here, the authors show that a CEP128 variant observed in human male siblings causes reduced sperm counts and morphologically abnormal sperm when modeled in mice, suggesting a role for CEP128 in male fertility.
- Xueguang Zhang
- , Lingbo Wang
- & Ying Shen
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Article
| Open AccessKastor and Polluks polypeptides encoded by a single gene locus cooperatively regulate VDAC and spermatogenesis
A number of testes-specific lncRNAs have been annotated but their roles remain largely unexplored. Here the authors identify two small peptides encoded by the lncRNA Gm9999, Kastor and Polluks, both of which are required for male fertility in mice.
- Shintaro Mise
- , Akinobu Matsumoto
- & Keiichi I. Nakayama
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Article
| Open AccessHuman reproduction is regulated by retrotransposons derived from ancient Hominidae-specific viral infections
The transcription factor network required for primordial germ cell (PGC) specification is known to diverge in mammals. Here the authors show that hominidae-specific transposable element (TE) LTR5Hs becomes transcriptionally active during PGC specification, and LTR5Hs inactivation abrogates human PGC specification
- Xinyu Xiang
- , Yu Tao
- & Amander T. Clark
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Article
| Open AccessDynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis
The domestic chicken Gallus gallus domesticus is a classic model for the study of folliculogenesis. Here the authors integrate multi-omics analyses characterizing the dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis.
- Diyan Li
- , Chunyou Ning
- & Mingzhou Li
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Article
| Open AccessMaintenance of quiescent oocytes by noradrenergic signals
Kim et al. show noradrenergic signaling for stress responses such as flight and fight, also serves as a conserved signal for maintaining oocyte quiescence under unfavorable conditions in worms, flies, and fish.
- Jeongho Kim
- , Moonjung Hyun
- & Young-Jai You
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Article
| Open AccessCell-fate transition and determination analysis of mouse male germ cells throughout development
The full-term developmental profile of male germ cells remains undefined. Here, the authors use single-cell sequencing to investigate the transcriptome landscapes of mouse male germ cells throughout development and find several critical regulators for prenatal cell-fate determination.
- Jiexiang Zhao
- , Ping Lu
- & Xiao-Yang Zhao
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Article
| Open AccessA somatic proteoglycan controls Notch-directed germ cell fate
Notch receptor GLP-1 is required for maintaining germ cells in the C. elegans germline. Here the authors show that syndecan-1, a somatic transmembrane proteoglycan regulates expression of glp-1 and germ cell mitosis in C. elegans, by promoting calcium-dependent binding of APTF-2 to the glp-1 promoter.
- Sandeep Gopal
- , Aqilah Amran
- & Roger Pocock
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Article
| Open AccessMammalian SWI/SNF chromatin remodeler is essential for reductional meiosis in males
The mammalian SWI/SNF nucleosome remodeler is required for spermatogenesis. Here, the authors show that PBAF is essential for meiotic cell division in males and required to activate the expression of critical genes involved in spindle assembly and nuclear division in spermatocytes.
- Debashish U. Menon
- , Oleksandr Kirsanov
- & Terry Magnuson
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Article
| Open AccessCENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes
Chromosome segregation is essential to avoid aneuploidy, yet in mammalian oocytes it progressively fails in an age-dependent manner. Here the authors identify CENP-V as a microtubule binding and bundling protein crucial to faithful oocyte meiosis, and present Cenp-V−/− oocytes as revealing age-dependent weakening of the spindle assembly checkpoint.
- Dalileh Nabi
- , Hauke Drechsler
- & Mariola Chacón
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Article
| Open AccessEnhancer-associated H3K4 methylation safeguards in vitro germline competence
While inductive signals controlling germline specification are well characterized, the intrinsic factors that allow epiblast cells to respond to such signals remain largely unknown. Here the authors use in vitro differentiated primordial germ cells to show that partial retention of histone H3K4 monomethylation within relevant enhancers is important for germline competence and specification.
- Tore Bleckwehl
- , Giuliano Crispatzu
- & Álvaro Rada-Iglesias
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Article
| Open AccessHecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles
Ribonucleoprotein (RNP) granules are responsible for mRNA transport and local translation required for neuronal and oocyte maturation. Here the authors show that loss of the Drosophila Ub ligase Hecw enlarges RNP granules, leads to a liquid to gel-like transition, and results in defective oogenesis and neuronal loss.
- Valentina Fajner
- , Fabio Giavazzi
- & Simona Polo
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Article
| Open AccessPre-meiotic 21-nucleotide reproductive phasiRNAs emerged in seed plants and diversified in flowering plants
Pre-meiotic anthers of monocots accumulate phased, small interfering RNAs (phasiRNAs) that are absent in many well-studied model eudicots. Here, the authors show that such 21-nt phasiRNAs are in fact present in diverse eudicot species including strawberry, in which production is triggered by miR11308.
- Suresh Pokhrel
- , Kun Huang
- & Blake C. Meyers
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Article
| Open AccessThe missing linker between SUN5 and PMFBP1 in sperm head-tail coupling apparatus
The sperm head-to-tail coupling apparatus ensures sperm head-tail integrity, but mechanistic insights remain limited. Here the authors demonstrate that CENTLEIN links and controls the interaction between SUN5 and PMFBP1, indicating that its impairments might be associated with acephalic spermatozoa syndrome.
- Ying Zhang
- , Chao Liu
- & Li Yuan
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Article
| Open AccessBisection of the X chromosome disrupts the initiation of chromosome silencing during meiosis in Caenorhabditis elegans
During meiosis, sex chromosomes show silenced gene expression that is disrupted when translocated to autosomes. Here, the authors engineer C. elegans with bisected X chromosomes and see active transcription in gonads, indicating continuity of sex chromosomes promotes silencing.
- Yisrael Rappaport
- , Hanna Achache
- & Yonatan B. Tzur
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Article
| Open AccessTCF21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice
Whether the adult testis harbours a somatic progenitor population is unknown. Here, the authors provide evidence that the testis interstitial cells expressing the transcription factor Tcf21 maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury.
- Yu-chi Shen
- , Adrienne Niederriter Shami
- & Saher Sue Hammoud
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Article
| Open AccessThe combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis
Although CTCF is a well-established 3D chromatin organizer in multicellular eukaryotes, relatively little is known about its male germ cell-specific paralogue, BORIS. Here the authors investigate how CTCF and BORIS interact and compensate in the male germline of mice to ensure appropriate activation of spermatogenesis-specific genes.
- Samuel Rivero-Hinojosa
- , Elena M. Pugacheva
- & Victor V. Lobanenkov
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Article
| Open AccessMeiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis
The authors add to our knowledge of the transcriptional regulation of the meiotic program in mice spermatocytes, showing ZFP541 regulates meiotic prophase and transition to the division phase by being the target for upstream factors MEIOSIN/STRA8.
- Yuki Horisawa-Takada
- , Chisato Kodera
- & Kei-Ichiro Ishiguro
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Article
| Open AccessThe SUN1-SPDYA interaction plays an essential role in meiosis prophase I
Telomeres attach to the nuclear envelope to facilitate homolog pairing during meiosis prophase I. Here, the authors show that SUN1 and SPDYA interact, and demonstrate that this interaction is important for telomere structure and function, and essential to mice gametogenesis.
- Yanyan Chen
- , Yan Wang
- & Ming Lei
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Article
| Open AccessOocyte-derived microvilli control female fertility by optimizing ovarian follicle selection in mice
How structural features on oocytes regulate mammalian female reproduction is unclear. Here, the authors provide imaging and physiological evidence (for example on Radixin knockout) to identify oocyte-derived mushroom-like microvilli that control the female reproductive lifespan by governing the fate of follicles.
- Yan Zhang
- , Ye Wang
- & Hua Zhang
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Article
| Open AccessDNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells
Caspase independent alternative cell death (ACD) pathways exist, but have been largely investigated under non-physiological conditions. Here, the authors show that Drosophila primordial germ cells normally elicit DNase II-dependent DNA damage, triggering a parthanatos-like ACD pathway.
- Lama Tarayrah-Ibraheim
- , Elital Chass Maurice
- & Eli Arama
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Article
| Open AccessThe M-phase regulatory phosphatase PP2A-B55δ opposes protein kinase A on Arpp19 to initiate meiotic division
Mechanisms triggering meiotic divisions of oocytes remain unclear. Here, the authors report that meiosis resumption relies on the timely phosphorylation of Arpp19 protein at two distinct sites, which depends on two kinases (PKA and Gwl) and a single phosphatase (PP2A-B55δ).
- Tom Lemonnier
- , Enrico Maria Daldello
- & Aude Dupré
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Article
| Open AccessNutrient restriction synergizes with retinoic acid to induce mammalian meiotic initiation in vitro
Retinoic acid is necessary but not sufficient to induce meiosis. Here, the authors use primary mouse undifferentiated spermatogonia culture to show that nutrient restriction, an inducer of yeast meiosis, combined with retinoic acid induces meiotic gene and chromosome programs in mammalian germ cells.
- Xiaoyu Zhang
- , Sumedha Gunewardena
- & Ning Wang
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Article
| Open AccessEpidermal growth factor receptor signaling uncouples germ cells from the somatic follicular compartment at ovulation
Uncoupling of mature oocytes from somatic granulosa cells is required for their fertilization. Here the authors show that activation of EGFR signalling in granulosa cells during ovulation triggers ERK-dependent loss of filopodia oocyte adhesion, and Arp2/3 mediated retraction of granulosa cell filopodia.
- Laleh Abbassi
- , Stephany El-Hayek
- & Hugh J. Clarke
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Article
| Open AccessGerm granule dysfunction is a hallmark and mirror of Piwi mutant sterility
Piwi deficiency results in sterility and is associated with transposon expression and genomic instability. Here the authors show that sterility of C. elegans Piwi prg-1 mutant is not associated with transposon-induced DNA damage but is associated with and is phenocopied by dysfunction of germ granules.
- Maya Spichal
- , Bree Heestand
- & Shawn Ahmed
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Article
| Open AccessBlastocyst complementation using Prdm14-deficient rats enables efficient germline transmission and generation of functional mouse spermatids in rats
The uptake of donor pluripotent stem cells (PSCs) in hosts of different species and subsequent germline transmission is very inefficient. Here, the authors show, using Prdm14 gene depleted rat host blastocysts to remove functional sperm, that germline transmission from donor rat or mouse PSCs is possible.
- Toshihiro Kobayashi
- , Teppei Goto
- & Masumi Hirabayashi
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Article
| Open AccessC. elegans germ granules require both assembly and localized regulators for mRNA repression
Nematode P granules are cytoplasmic RNA–protein biomolecule condensates central to germ cell development. Here the authors show that dimerization of the PGL-1 scaffolding protein is crucial to granule formation and mRNA repression, and that the WAGO-1 Argonaute protein is a cofactor in repressing PGL-1 bound mRNAs.
- Scott Takeo Aoki
- , Tina R. Lynch
- & Judith Kimble
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Article
| Open AccessDynamic sex chromosome expression in Drosophila male germ cells
Sex chromosome gene content and expression is unusual. Here the authors use single cell RNA-Seq on Drosophila larvae to demonstrate that the single X and pair of 4th chromosomes are specifically inactivated in primary spermatocytes, while genes on the single Y chromosome become maximally active in primary spermatocytes.
- Sharvani Mahadevaraju
- , Justin M. Fear
- & Brian Oliver
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Article
| Open AccessSingle-cell analysis of Schistosoma mansoni identifies a conserved genetic program controlling germline stem cell fate
Our understanding of how the germline of the parasitic flatworm Schistosoma mansoni develops is limited. Here, the authors use single cell RNAseq and functional genomic analysis of juvenile worms to identify a regulatory program that mediates the fate of germline stem cells between proliferation and differentiation.
- Pengyang Li
- , Dania Nanes Sarfati
- & Bo Wang
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Article
| Open AccessThe p63 C-terminus is essential for murine oocyte integrity
The transcription factor p63 mediates different cellular responses affecting epithelial and oocyte biology. Here, the authors generate a mouse model (HET Δ13p63 mice) expressing the p63β isoform and show this affects ovary development, phenocopying a human syndrome, primary ovary insufficiency.
- Anna Maria Lena
- , Valerio Rossi
- & Eleonora Candi
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Article
| Open AccessLong first exons and epigenetic marks distinguish conserved pachytene piRNA clusters from other mammalian genes
The pachytene piRNA loci are transcribed by RNA polymerase II in the male germline of placental mammals. Here the authors show that a long first exon or a long unspliced transcript correlates with germline-specific production of piRNA precursor transcripts and mature piRNAs.
- Tianxiong Yu
- , Kaili Fan
- & Zhiping Weng
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Article
| Open AccessPRC2 and EHMT1 regulate H3K27me2 and H3K27me3 establishment across the zygote genome
Dynamic arrangement of epigenetic modifications such as repressive H3K27 methylation is essential for zygote development. Here the authors show that establishment of genome-wide H3K27me3 in zygotes requires EZH2, that EZH1 partially compensates for EZH2 loss, and that EHMT1 is involved in H3K27me2 establishment.
- Tie-Gang Meng
- , Qian Zhou
- & Qing-Yuan Sun
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Article
| Open AccessReconstitution of prospermatogonial specification in vitro from human induced pluripotent stem cells
Spermatogonia establishment in the fetal and postnatal period is essential for spermatozoa production. Here the authors present a protocol for in vitro reconstitution of human prospermatogonial specification and perform single cell RNA-sequencing to delineate lineage trajectories.
- Young Sun Hwang
- , Shinnosuke Suzuki
- & Kotaro Sasaki
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Article
| Open AccessCollectively stabilizing and orienting posterior migratory forces disperses cell clusters in vivo
During development, primordial germ cell clusters undergo dispersal but how cell–cell adhesion and contractility are coordinated during this process in vivo is unclear. Here, the authors show that Drosophila primordial germ cells utilize migratory forces to disperse through G-protein coupled receptor mediated collective guidance of front-back polarity outwards from the cluster.
- B. Lin
- , J. Luo
- & R. Lehmann
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Article
| Open AccessGeneration, localization and functions of macrophages during the development of testis
The developmental origins and functions of testis macrophages remain incompletely characterized. Here, the authors show, using histology, high-dimensional mass cytometry and cell fate-mapping data, that interstitial and peritubular macrophages originate from distinct precursors and contribute distinctly to spermatogenesis.
- Emmi Lokka
- , Laura Lintukorpi
- & Marko Salmi
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Article
| Open AccessTEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing
The PIWI protein MIWI2 counteracts transposon activity by transcriptional silencing in the mammalian germline. Here, the authors show that TEX15 interacts with MIWI2 and is required for piRNA-directed methylation of transposable elements in male germ cells.
- Theresa Schöpp
- , Ansgar Zoch
- & Dónal O’Carroll
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Article
| Open AccessEpigenetic homogeneity in histone methylation underlies sperm programming for embryonic transcription
In addition to paternal genetic material, sperm contributes epigenetic information to the embryo to efficiently support development. Here, the authors demonstrate a homogeneous paternal contribution to epigenetic information via sperm-derived modified histone transmission to the developing vertebrate embryo.
- Mami Oikawa
- , Angela Simeone
- & Jerome Jullien
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Article
| Open AccessmiR2118-dependent U-rich phasiRNA production in rice anther wall development
MicroRNA2118 induces the production of phased small interfering RNAs (phaisRNAs) in plants. Here the authors show that rice miR2118 is required for both male and female fertility and supports the production of atypical U-rich 21 nt phasiRNAs that are abundant in anther walls.
- Saori Araki
- , Ngoc Tu Le
- & Reina Komiya
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Article
| Open AccessThe BCL-2 pathway preserves mammalian genome integrity by eliminating recombination-defective oocytes
If left unrepaired, meiotic DSBs are toxic to mammalian cells, thus oocytes in which DSBs persist are eliminated by the DNA-damage checkpoint. Here the authors provide insights into the roles of PUMA, NOXA and BAX during DNA damage checkpoint that eliminates Dmc1−/− and Msh5−/− oocytes.
- Elias ElInati
- , Agata P. Zielinska
- & James M. A. Turner
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Article
| Open AccessPtch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration
How co-receptors Gas1 and Boc interact with Ptch1/2 receptors and regulate Hh signalling is unclear. Here, the authors demonstrate that the spatiotemporal expression of Gas1 and Boc determines how Hh signalling affects the dynamic migration of murine primordial germ cells.
- Yeonjoo Kim
- , Jiyoung Lee
- & Soo-Hyun Kim
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Article
| Open AccessA critical role of PRDM14 in human primordial germ cell fate revealed by inducible degrons
PRDM14 is a critical transcription factor for mouse primordial germ cell specification, but its role in human remains unclear. Here, PRDM14 protein depletion using auxin-inducible degron uncovers a critical role for human germ cell specification, but regulation of a different set of target genes than in mouse.
- Anastasiya Sybirna
- , Walfred W. C. Tang
- & M. Azim Surani
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Article
| Open AccessMaximizing the ovarian reserve in mice by evading LINE-1 genotoxicity
Mammals lose up to 80% of their finite oocyte supply during fetal development. Here the authors interrogate mechanisms of fetal oocyte attrition in mice, driven by the simultaneous upregulation of LINE-1 retrotransposon activity and inhibit these mechanisms to increase the functional ovarian reserve.
- Marla E. Tharp
- , Safia Malki
- & Alex Bortvin
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Article
| Open AccessProgrammed DNA elimination of germline development genes in songbirds
Songbirds have extensive germline–soma genome differences due to developmental elimination of a germline-specific chromosome (GRC). Here, the authors show that the GRC contains dozens of expressed developmental genes, some of which have been on the GRC since the ancestor of all songbirds.
- Cormac M. Kinsella
- , Francisco J. Ruiz-Ruano
- & Alexander Suh
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Article
| Open AccessSertoli cell-only phenotype and scRNA-seq define PRAMEF12 as a factor essential for spermatogenesis in mice
Spermatogonial stem cells have the dual capacity to self-renew and differentiate into mature spermatozoa. Here, using transcriptome analyses of juvenile testes in gene-edited mice, the authors demonstrate that PRAMEF12 is required to maintain germ cell homeostasis and promote their differentiation.
- Zhengpin Wang
- , Xiaojiang Xu
- & Jurrien Dean
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Article
| Open AccessPhosphatidylserine on viable sperm and phagocytic machinery in oocytes regulate mammalian fertilization
Izumo and Juno are receptors on sperm and eggs respectively required for fusion, but other factors for sperm-egg fusion are poorly studied. Here, the authors report that phosphatidylserine, found mainly on cells marked for death, is also present on motile sperm, recognized by egg receptors, and is required for sperm-egg fusion.
- Claudia M. Rival
- , Wenhao Xu
- & Kodi S. Ravichandran
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Article
| Open AccessEZHIP constrains Polycomb Repressive Complex 2 activity in germ cells
Polycomb Repressive Complex 2 (PRC2) plays critical roles in transcriptional silencing during development. Here the authors identify EZHIP as a cofactor of PRC2 expressed predominantly in the gonads, finding that EZHIP limits the enzymatic activity of PRC2 in germ cells in mice.
- Roberta Ragazzini
- , Raquel Pérez-Palacios
- & Raphaël Margueron
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Article
| Open AccessMeiosis I progression in spermatogenesis requires a type of testis-specific 20S core proteasome
Proteasomal degradation is required for the progression of spermatogenesis. Here the authors demonstrate that deletion of the testis-specific proteasome subunit PMSA8 leads to stabilization of the meiotic proteins RAD51 and RPA1 and a spermatogenic block at M-phase of meiosis I.
- Qianting Zhang
- , Shu-Yan Ji
- & Chao Yu
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Article
| Open AccessZebrafish preserve global germline DNA methylation while sex-linked rDNA is amplified and demethylated during feminisation
Germline cells transfer genetic information to offspring, and in zebrafish, drive sex determination. Here the authors report that, unlike mammals, the germline of zebrafish does not undergo genome-wide DNA methylation erasure, while amplifying and demethylating sex-linked rDNA during feminisation.
- Oscar Ortega-Recalde
- , Robert C. Day
- & Timothy A. Hore
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Article
| Open AccessMolecular basis of egg coat cross-linking sheds light on ZP1-associated female infertility
Glycoprotein ZP1 is a component of the oocyte’s zona pellucida (ZP), and mutations in human ZP1 are linked to female infertility. Here, using structure-function analysis, the authors suggest that filament cross-linking by ZP1 is required to form a stable ZP in human, and infertility mutations interfere with cross-linking.
- Kaoru Nishimura
- , Elisa Dioguardi
- & Luca Jovine
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Article
| Open AccessRetention of paternal DNA methylome in the developing zebrafish germline
Germ cells are the means of transferring genetic information to the next generation. Here the authors characterise the DNA methylomes of zebrafish primordial germ cells and find that, unlike mammals, the zebrafish germ cells do not undergo genome-wide DNA demethylation but rather retain paternal DNA methylation patterns
- Ksenia Skvortsova
- , Katsiaryna Tarbashevich
- & Ozren Bogdanovic