Featured
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Article
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Diffusible fraction of niche BMP ligand safeguards stem-cell differentiation
The activity of Drosophila male germline stem cells is tightly regulated by a cluster of somatic niche cells. Here they find that Dpp induces opposed cellular responses in stem cells versus in differentiating descendants, thereby ensuring spatial control of the niche with a single factor.
- Sharif M. Ridwan
- , Autumn Twillie
- & Mayu Inaba
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Article
| Open Access
RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis
Gene expression dynamics are tightly regulated during spermatogenesis, with disruptions resulting in infertility. Here they identify a critical role for RNA PolII pausing in spermatogenesis and show that loss of the RNA PolII pausing factor NELF causes meiotic arrest.
- Emily G. Kaye
- , Kavyashree Basavaraju
- & Prabhakara P. Reddi
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Article
| Open Access
The evolution of centriole degradation in mouse sperm
Centrioles have a conserved structure and function but have diversified in sperm. Here the authors provide insight into the molecular mechanisms and adaptive evolution underlying this diversification.
- Sushil Khanal
- , Ankit Jaiswal
- & Tomer Avidor-Reiss
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Article
| Open Access
STYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation
The sperm flagellum is composed of tubulin-based microtubules and is critical for sperm motility and thus male fertility. Here, the authors show that STYXL1 regulates CCT complex-facilitated tubulin folding and is essential for sperm flagella formation.
- Yu Chen
- , Mengjiao Luo
- & Xuejiang Guo
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Article
| Open Access
Metabolic regulation of proteome stability via N-terminal acetylation controls male germline stem cell differentiation and reproduction
How cellular metabolism is connected to differentiation remains poorly understood. Here the authors report a regulatory cascade in which circulating citrate regulates sperm production by controlling protein stability via a specific protein post-translational modification.
- Charlotte M. François
- , Thomas Pihl
- & Bruno Hudry
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Article
| Open Access
The non-redundant functions of PIWI family proteins in gametogenesis in golden hamsters
The role of PIWI proteins in mammalian reproduction remains poorly understood. Here, using golden hamsters, the authors establish expression profiles for all four PIWIs during gametogenesis and characterize their associated reproductive defects.
- Xiaolong Lv
- , Wen Xiao
- & Ligang Wu
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Article
| Open Access
SYPL1 defines a vesicular pathway essential for sperm cytoplasmic droplet formation and male fertility
The cytoplasmic droplet is an elusive structure of mammalian sperm. Here, the authors uncover a key gene that defines a vesicular pathway essential for cytoplasmic droplet formation and male fertility.
- Jiali Liu
- , Louis Hermo
- & Chen Chen
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Article
| Open Access
Biophysical ordering transitions underlie genome 3D re-organization during cricket spermiogenesis
Orsi et al. identify an elegant solution to DNA packing in cricket sperm nuclei, whereby relatively simple biophysical changes in chromatin properties result in a liquid crystal-like twisted spool organization that favors ultracompaction.
- Guillermo A. Orsi
- , Maxime M. C. Tortora
- & Benjamin Loppin
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Article
| Open Access
Broad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility
Testis-specific serine/threonine kinases have been associated with male infertility, but the mechanism for this connection is unclear. Here they identify a Drosophila homolog, dTSSK, which is essential for male fertility in fruit flies and has functionally conserved catalytic activity with human TSSKs.
- Xuedi Zhang
- , Ju Peng
- & Guanjun Gao
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Article
| Open Access
Single-cell RNA-seq uncovers dynamic processes orchestrated by RNA-binding protein DDX43 in chromatin remodeling during spermiogenesis
Germ cells undergo dramatic chromatin and transcriptomic changes during spermatogenesis, though how this is controlled is not well established. Here they show that RNA-binding protein DDX43 directs the spermatid differentiation trajectory and regulates chromatin remodeling in spermiogenesis, which is partially mediated by its target gene Elfn2.
- Huanhuan Tan
- , Weixu Wang
- & Ke Zheng
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Article
| Open Access
A small secreted protein NICOL regulates lumicrine-mediated sperm maturation and male fertility
Mammalian sperm need to be matured in the epididymis to achieve potential for fertility. Here the authors identify NICOL as a secreted protein that acts on the epididymis to trigger its functional differentiation and induce sperm maturation.
- Daiji Kiyozumi
- , Kentaro Shimada
- & Masahito Ikawa
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Article
| Open Access
ARRDC5 expression is conserved in mammalian testes and required for normal sperm morphogenesis
Male organisms produce huge numbers of sperm each day, with defects in the process resulting infertility. Here they show that arrestin domain-containing 5 (ARRDC5) is a testis-specific molecule required for mammalian spermatogenesis.
- Mariana I. Giassetti
- , Deqiang Miao
- & Jon M. Oatley
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Perspective
| Open Access
Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development
Increasing evidence suggests parental environmental stressors can influence offspring health and disease outcomes. In this perspective, the authors provide an update of the paternal epigenetic inheritance field and propose links between paternally transmitted epigenetic influences and functional changes to the embryo.
- Ariane Lismer
- & Sarah Kimmins
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Article
| Open Access
A-MYB and BRDT-dependent RNA Polymerase II pause release orchestrates transcriptional regulation in mammalian meiosis
During spermatogenic meiosis, chromatin changes due to transcription, homologous recombination, and chromosome synapsis must be coordinated. Here they show that A-MYC and BRDT regulate release of paused RNA PolII to induce a transcriptional burst during pachytene of prophase I.
- Adriana K. Alexander
- , Edward J. Rice
- & Charles G. Danko
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Article
| Open Access
Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity
Male meiosis relies on canonical centrosomes for spindle formation, but how this differs from acentrosomal oocyte meiosis is unclear. Here they show that spindle formation in sperm relies on DYNLRB2, similar to the activity of DYNLRB1 in mitotic cells.
- Shuwen He
- , John P. Gillies
- & Hiroki Shibuya
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Article
| Open Access
The m6A reader PRRC2A is essential for meiosis I completion during spermatogenesis
Modification of RNA with m6A has been shown to be important during spermatogenesis. Here they identify post-transcriptional functions of PRRC2A, showing it promotes transcriptome transition from spermatogonia to spermatocytes and the translation of genes related to cell division.
- Xinshui Tan
- , Caihong Zheng
- & Fengchao Wang
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Article
| Open Access
Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation
Here the authors show that active DNA damage response signaling is required both to initiate and maintain meiotic sex chromosome inactivation via a dynamic and reversible process.
- Hironori Abe
- , Yu-Han Yeh
- & Satoshi H. Namekawa
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Article
| Open Access
TOPOVIBL-REC114 interaction regulates meiotic DNA double-strand breaks
TOPOVIBL and REC114 are required for meiotic DNA double-strand breaks (DSBs). This study shows that TOPOVIBL forms a complex with REC114 and mice carrying mutations that disrupt the interaction show DSB defects with distinct outcomes in males and females.
- Alexandre Nore
- , Ariadna B. Juarez-Martinez
- & Bernard de Massy
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Article
| Open Access
Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing
The regulatory mechanisms contributing to male reproductive ageing are unknown. Here, the authors show that Nestin-dependent mito-ER contacts (MERCs) regulate stem Leydig cell (SLC) senescence and provide insights into SLCs-targeting therapies.
- Senyu Yao
- , Xiaoyue Wei
- & Jiancheng Wang
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Article
| Open Access
BMP4 drives primed to naïve transition through PGC-like state
Multiple pluripotent states have been described in mouse and human stem cells. Here the authors describe trajectories during BMP4 induced primed to naïve transition, which bifurcates into naïve and trophoblast-like branches with a PGC-like intermediate at the naïve branch.
- Shengyong Yu
- , Chunhua Zhou
- & Jing Liu
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Article
| Open Access
3D chromatin remodelling in the germ line modulates genome evolutionary plasticity
The role of genome folding in the heritability and evolvability of structural variations is not well understood. Here the authors investigate the impact of the three-dimensional genome topology of germ cells in the formation and transmission of gross structural genomic changes detected from comparing whole-genome sequences of 14 rodent species.
- Lucía Álvarez-González
- , Frances Burden
- & Aurora Ruiz-Herrera
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Article
| Open Access
Distinctive molecular features of regenerative stem cells in the damaged male germline
Male germline regeneration after damage is dependent on spermatogonial stem cells (SSCs) but pathways mediating the regenerative response are unclear. Here the authors define roles for growth factor signalling and mTORC1 in SSC-driven regeneration.
- Hue M. La
- , Jinyue Liao
- & Robin M. Hobbs
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Article
| Open Access
CEP128 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 Access
Kastor 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 Access
Human 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 Access
Mammalian 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 Access
The 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 Access
The 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 Access
Meiosis-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 Access
Dynamic 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 Access
Long 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 Access
Reconstitution 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 Access
Generation, 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 Access
TEX15 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 Access
Epigenetic 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 Access
Sertoli 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 Access
DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia
Sustained sperm production is dependent on activity of undifferentiated spermatogonia. Here, the authors demonstrate an essential role for RNA helicase DDX5 in maintenance of spermatogonia in adults through control of gene transcription plus RNA processing and export.
- Julien M. D. Legrand
- , Ai-Leen Chan
- & Robin M. Hobbs
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Article
| Open Access
Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche
Human embryonic stem cells can be differentiated in vitro into primordial germ cell-like cells (PGCLCs) that resemble early primordial germ cells (PGCs). Here the authors transplant PGCLCs generated from rhesus macaque iPSCs into mouse and rhesus macaque seminiferous tubules, which matures these into late PGCs and spermatogonia-like cells.
- Enrique Sosa
- , Di Chen
- & Amander T. Clark
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Article
| Open Access
Caenorhabditis elegans sperm carry a histone-based epigenetic memory of both spermatogenesis and oogenesis
Paternal contributions to epigenetic inheritance via nucleosomes are poorly understood, as sperm in many organisms replace the majority of nucleosomes with protamines. Here the authors provide evidence that Caenorhabditis elegans sperm retain histone packaging of the genome and provide a histone-based epigenetic memory that is important for germ cell development in offspring.
- Tomoko M. Tabuchi
- , Andreas Rechtsteiner
- & Susan Strome
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Article
| Open Access
ATR is a multifunctional regulator of male mouse meiosis
ATR kinase is required for meiosis in non-mammalian model organisms. Here the authors demonstrate, using a tissue-specific knockout approach, that ATR is also essential for male meiosis in mouse, regulating meiotic recombination and synapsis.
- Alexander Widger
- , Shantha K. Mahadevaiah
- & James M.A. Turner
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Article
| Open Access
ATR is required to complete meiotic recombination in mice
ATR kinase is required for meiosis in non-mammalian model organisms. Here the authors demonstrate, using a hypomorphic Atr mutation and chemical inhibition, that ATR is also essential for male meiosis in mouse, regulating meiotic recombination and synapsis.
- Sarai Pacheco
- , Andros Maldonado-Linares
- & Ignasi Roig
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Article
| Open Access
A novel atypical sperm centriole is functional during human fertilization
The two zygote centrioles are paternally inherited; however, their development is incompletely understood. Here, the authors show that the distal centriole is remodeled into an atypical centriole which functions as the zygote’s second centriole.
- Emily L. Fishman
- , Kyoung Jo
- & Tomer Avidor-Reiss
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Article
| Open Access
TDRD5 binds piRNA precursors and selectively enhances pachytene piRNA processing in mice
Pachytene piRNAs are abundant piRNAs in mammalian adult testes but their biogenesis pathway is not fully understood. Here, the authors identify TDRD5 as a piRNA biogenesis factor in mice, showing that it binds piRNA precursors and promotes pachytene piRNA production from specific transcript regions.
- Deqiang Ding
- , Jiali Liu
- & Chen Chen
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Review Article
| Open Access
The emergence of piRNAs against transposon invasion to preserve mammalian genome integrity
Transposable elements can be activated during germ cell maturation, potentially leading to genome instability and rewiring of the genetic circuitry. In this review, the authors discuss how the piRNA machinery suppresses these elements to ensure accurate spermatogenesis.
- Christina Ernst
- , Duncan T. Odom
- & Claudia Kutter
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Article
| Open Access
PNLDC1 is essential for piRNA 3′ end trimming and transposon silencing during spermatogenesis in mice
piRNAs are regulatory RNAs that play a critical role in transposon silencing and gametogenesis. Here, the authors provide evidence that mammalian PNLDC1 is a regulator of piRNA biogenesis, transposon silencing and spermatogenesis, protecting the germline genome in mice.
- Deqiang Ding
- , Jiali Liu
- & Chen Chen
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Article
| Open Access
Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells
Although phagocytic clearance of apoptotic germ cells by Sertoli cells is essential for spermatogenesis, little of the mechanism is known. Here the authors show that Sertoli cells employ LC3-associated phagocytosis (LAP) by recruiting autophagy member proteins to clear apoptotic germ cells.
- Subbarayalu Panneerdoss
- , Suryavathi Viswanadhapalli
- & Manjeet K. Rao
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Article
| Open Access
NEDD4 controls spermatogonial stem cell homeostasis and stress response by regulating messenger ribonucleoprotein complexes
Stress granules (SG) comprise aggregates of cellular messenger ribonucleoproteins (mRNPs) but how they form is unclear. Here, the authors identify NEDD4, an E3 ubiquitin ligase, as regulating the RNA binding protein NANOS2 and turnover of mRNP components, and so SG disassembly in spermatogonial stem cells.
- Zhi Zhou
- , Hiroshi Kawabe
- & Yumiko Saga
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Article
| Open Access
C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility
The synaptonemal complex is a meiosis-specific proteinaceous structure that supports homologous chromosome pairs during meiosis. Here, the authors show that SIX6OS1 (of previously unknown function) is part of the synaptonemal complex central element and upon deletion in mice, causes defective chromosome synapsis and infertility.
- Laura Gómez-H
- , Natalia Felipe-Medina
- & Alberto M. Pendas
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Article
| Open Access
Male-killing symbiont damages host’s dosage-compensated sex chromosome to induce embryonic apoptosis
Symbiotic bacteria are able to interfere with host reproduction in ways that are detrimental to the host organism. Here the authors show that Spiroplasma induces DNA damage on the male X chromosome in Drosophila, causing sex-specific apoptosis.
- Toshiyuki Harumoto
- , Hisashi Anbutsu
- & Takema Fukatsu
Atypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions