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  • 1
    Online Resource
    Online Resource
    Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline
    The Company of Biologists ; 2012
    In:  Development Vol. 139, No. 19 ( 2012-10-01), p. 3623-3632
    Details
    In: Development, The Company of Biologists, Vol. 139, No. 19 ( 2012-10-01), p. 3623-3632
    Abstract: Mouse primordial germ cells (PGCs) erase global DNA methylation (5mC) as part of the comprehensive epigenetic reprogramming that occurs during PGC development. 5mC plays an important role in maintaining stable gene silencing and repression of transposable elements (TE) but it is not clear how the extensive loss of DNA methylation impacts on gene expression and TE repression in developing PGCs. Using a novel epigenetic disruption and recovery screen and genetic analyses, we identified a core set of germline-specific genes that are dependent exclusively on promoter DNA methylation for initiation and maintenance of developmental silencing. These gene promoters appear to possess a specialised chromatin environment that does not acquire any of the repressive H3K27me3, H3K9me2, H3K9me3 or H4K20me3 histone modifications when silenced by DNA methylation. Intriguingly, this methylation-dependent subset is highly enriched in genes with roles in suppressing TE activity in germ cells. We show that the mechanism for developmental regulation of the germline genome-defence genes involves DNMT3B-dependent de novo DNA methylation. These genes are then activated by lineage-specific promoter demethylation during distinct global epigenetic reprogramming events in migratory (∼E8.5) and post-migratory (E10.5-11.5) PGCs. We propose that genes involved in genome defence are developmentally regulated primarily by promoter DNA methylation as a sensory mechanism that is coupled to the potential for TE activation during global 5mC erasure, thereby acting as a failsafe to ensure TE suppression and maintain genomic integrity in the germline.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    URL: Article
    DOI: 10.1242/dev.081661
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2012
    detail.hit.zdb_id: 2007916-3
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Sexually dimorphic development of mouse primordial germ cells: switching from oogenesis to spermatogenesis
    The Company of Biologists ; 2002
    In:  Development Vol. 129, No. 5 ( 2002-03-01), p. 1155-1164
    Details
    In: Development, The Company of Biologists, Vol. 129, No. 5 ( 2002-03-01), p. 1155-1164
    Abstract: During embryogenesis, primordial germ cells (PGCs) have the potential to enter either spermatogenesis or oogenesis. In a female genital ridge, or in a non-gonadal environment, PGCs develop as meiotic oocytes. However, male gonadal somatic cells inhibit PGCs from entering meiosis and direct them to a spermatogenic fate. We have examined the ability of PGCs from male and female embryos to respond to the masculinising environment of the male genital ridge, defining a temporal window during which PGCs retain a bipotential fate. To help understand how PGCs respond to the male gonadal environment, we have identified molecular differences between male PGCs that are committed to spermatogenesis and bipotential female PGCs. Our results suggest that one way in which PGCs respond to this masculinising environment is to synthesise prostaglandin D2. We show that this signalling molecule can partially masculinise female embryonic gonads in culture, probably by inducing female supporting cells to differentiate into Sertoli cells. In the developing testis, prostaglandin D2 may act as a paracrine factor to induce Sertoli cell differentiation. Thus part of the response of PGCs to the male gonadal environment is to generate a masculinising feedback loop to ensure male differentiation of the surrounding gonadal somatic cells.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    URL: Article
    DOI: 10.1242/dev.129.5.1155
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2002
    detail.hit.zdb_id: 2007916-3
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    SPC72: a spindle pole component required for spindle orientation in the yeast Saccharomyces cerevisiae
    The Company of Biologists ; 1998
    In:  Journal of Cell Science Vol. 111, No. 18 ( 1998-09-15), p. 2809-2818
    Details
    In: Journal of Cell Science, The Company of Biologists, Vol. 111, No. 18 ( 1998-09-15), p. 2809-2818
    Abstract: The monoclonal antibody 78H6 recognises an 85 kDa component of the yeast spindle pole body. Here we identify and characterise this component as Spc72p, the product of YAL047C. The sequence of SPC72 contains potential coiled-coil domains; its overexpression induced formation of large polymers that were strictly localised at the outer plaque and at the bridge of the spindle pole body. Immunoelectron microscopy confirmed that Spc72p was a component of these polymers. SPC72 was found to be non-essential for cell growth, but its deletion resulted in abnormal spindle positioning, aberrant nuclear migration and defective mating capability. Precisely, deletion of SPC72 resulted in a decreased number of astral microtubules: early in the cell cycle only few were detectable, and these were unattached to the spindle pole body in small-budded cells. Later in the cell cycle few, if any, remained, and they were unable to align the spindle properly. We conclude that Spc72p is not absolutely required for nucleation per se, but is needed for normal abundance and stability of astral microtubules.
    Type of Medium: Online Resource
    ISSN: 0021-9533 , 1477-9137
    URL: Article
    DOI: 10.1242/jcs.111.18.2809
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 1998
    detail.hit.zdb_id: 219171-4
    detail.hit.zdb_id: 1483099-1
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Sdmg1 is a conserved transmembrane protein associated with germ cell sex determination and germline-soma interactions in mice
    The Company of Biologists ; 2008
    In:  Development Vol. 135, No. 8 ( 2008-04-15), p. 1415-1425
    Details
    In: Development, The Company of Biologists, Vol. 135, No. 8 ( 2008-04-15), p. 1415-1425
    Abstract: In mammals, the supporting cell lineage in an embryonic gonad communicates the sex-determining decision to various sexually dimorphic cell types in the developing embryo, including the germ cells. However, the molecular nature of the sex-determining signals that pass from the supporting cells to the germ cells is not well understood. We have identified a conserved transmembrane protein, Sdmg1, owing to its male-specific expression in mouse embryonic gonads. Sdmg1 is expressed in the Sertoli cells of embryonic testes from 12.5 dpc, and in granulosa cells of growing follicles in adult ovaries. In Sertoli cells, Sdmg1 is localised to endosomes, and knock-down of Sdmg1 in Sertoli cell lines causes mis-localisation of the secretory SNARE Stx2 and defects in membrane trafficking. Upregulation of Sdmg1appears to be part of a larger programme of changes to membrane trafficking pathways in embryonic Sertoli cells, and perturbing secretion in male embryonic gonads in organ culture causes male-to-female germ cell sex reversal. These data suggest that changes that occur in the cell biology of embryonic Sertoli cells may facilitate the communication of male sex-determining decisions to the germ cells during embryonic development.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    URL: Article
    DOI: 10.1242/dev.019497
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2008
    detail.hit.zdb_id: 2007916-3
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    The impact of transposable elements on mammalian development
    The Company of Biologists ; 2016
    In:  Development Vol. 143, No. 22 ( 2016-11-15), p. 4101-4114
    Details
    In: Development, The Company of Biologists, Vol. 143, No. 22 ( 2016-11-15), p. 4101-4114
    Abstract: Despite often being classified as selfish or junk DNA, transposable elements (TEs) are a group of abundant genetic sequences that have a significant impact on mammalian development and genome regulation. In recent years, our understanding of how pre-existing TEs affect genome architecture, gene regulatory networks and protein function during mammalian embryogenesis has dramatically expanded. In addition, the mobilization of active TEs in selected cell types has been shown to generate genetic variation during development and in fully differentiated tissues. Importantly, the ongoing domestication and evolution of TEs appears to provide a rich source of regulatory elements, functional modules and genetic variation that fuels the evolution of mammalian developmental processes. Here, we review the functional impact that TEs exert on mammalian developmental processes and discuss how the somatic activity of TEs can influence gene regulatory networks.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    URL: Article
    DOI: 10.1242/dev.132639
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2016
    detail.hit.zdb_id: 2007916-3
    SSG: 12
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