129 research outputs found

    Not so non-marine? Revisiting the Stoer Group and the Mesoproterozoic biosphere

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    Funding for this project was provided by the NASA postdoctoral program (EES), the Lewis and Clark Fund (EES), an NSERC PGS-D grant (EJB), the NSF ELT (TWL, NJP) and FESD (TWL) programs, and the NASA Astrobiology Institute (TWL, NJP).The Poll a’Mhuilt Member of the Stoer Group (Torridonian Supergroup) in Scotland has been heralded as a rare window into the ecology of Mesoproterozoic terrestrial environments. Its unusually high molybdenum concentrations and large sulphur isotope fractionations have been used as evidence to suggest that lakes 1.2 billion years ago were better oxygenated and enriched in key nutrients relative to contemporaneous oceans, making them ideal habitats for the evolution of eukaryotes. Here we show with new Sr and Mo isotope data, supported by sedimentological evidence, that the depositional setting of this unit was likely connected to the ocean and that the elevated Mo and S contents can be explained by evapo-concentration of seawater. Thus, it remains unresolved if Mesoproterozoic lakes were important habitats for early eukaryotic life.Publisher PDFPeer reviewe

    The Doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1

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    The mechanisms that determine whether a neural progenitor cell (NPC) re-enters the cell cycle or exits and differentiates are pivotal for generating cells in correct numbers and diverse types, and hence dictate proper brain development. Combining gain-of-function and loss-of-function approaches in an embryonic stem cell-derived cortical differentiation model, we report that Dmrta2 plays an important role in maintaining NPCs in the cell cycle. Temporally controlled expression of transgenic Dmrta2 in NPCs suppresses differentiation without affecting their neurogenic competence. In contrast, Dmrta2 knockout accelerates the cell cycle exit and differentiation into post-mitotic neurons of NPCs derived from embryonic stem cells and in Emx1-cre conditional mutant mice. Dmrta2 function was linked to the regulation of Hes1 and other proneural genes as demonstrated by genome wide RNAseq and direct binding of Dmrta2 to the Hes1 genomic locus. Moreover, transient Hes1 expression rescues precocious neurogenesis in Dmrta2 knockout NPCs. Our study therefore establishes a novel link between Dmrta2 modulation of Hes1 expression and the maintenance of NPCs during cortical development.

    Systematic mapping of rRNA 2'-O methylation during frog development and involvement of the methyltransferase Fibrillarin in eye and craniofacial development in Xenopus laevis..

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    peer reviewedRibosomes are essential nanomachines responsible for protein production. Although ribosomes are present in every living cell, ribosome biogenesis dysfunction diseases, called ribosomopathies, impact particular tissues specifically. Here, we evaluate the importance of the box C/D snoRNA-associated ribosomal RNA methyltransferase fibrillarin (Fbl) in the early embryonic development of Xenopus laevis. We report that in developing embryos, the neural plate, neural crest cells (NCCs), and NCC derivatives are rich in fbl transcripts. Fbl knockdown leads to striking morphological defects affecting the eyes and craniofacial skeleton, due to lack of NCC survival caused by massive p53-dependent apoptosis. Fbl is required for efficient pre-rRNA processing and 18S rRNA production, which explains the early developmental defects. Using RiboMethSeq, we systematically reinvestigated ribosomal RNA 2'-O methylation in X. laevis, confirming all 89 previously mapped sites and identifying 15 novel putative positions in 18S and 28S rRNA. Twenty-three positions, including 10 of the new ones, were validated orthogonally by low dNTP primer extension. Bioinformatic screening of the X. laevis transcriptome revealed candidate box C/D snoRNAs for all methylated positions. Mapping of 2'-O methylation at six developmental stages in individual embryos indicated a trend towards reduced methylation at specific positions during development. We conclude that fibrillarin knockdown in early Xenopus embryos causes reduced production of functional ribosomal subunits, thus impairing NCC formation and migration

    DMRT5, DMRT3, and EMX2 Cooperatively Repress at the Pallium-Subpallium Boundary to Maintain Cortical Identity in Dorsal Telencephalic Progenitors

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    Specification of dorsoventral regional identity in progenitors of the developing telencephalon is a first pivotal step in the development of the cerebral cortex and basal ganglia. Previously, we demonstrated that the two zinc finger doublesex and mab-3 related (Dmrt) genes, Dmrt5 (Dmrta2) and Dmrt3, which are coexpressed in high caudomedial to low rostrolateral gradients in the cerebral cortical primordium, are separately needed for normal formation of the cortical hem, hippocampus, and caudomedial neocortex. We have now addressed the role of Dmrt3 and Dmrt5 in controlling dorsoventral division of the telencephalon in mice of either sex by comparing the phenotypes of single knock-out (KO) with double KO embryos and by misexpressing Dmrt5 in the ventral telencephalon. We find that DMRT3 and DMRT5 act as critical regulators of progenitor cell dorsoventral identity by repressing ventralizing regulators. Early ventral fate transcriptional regulators expressed in the dorsal lateral ganglionic eminence, such as Gsx2, are upregulated in the dorsal telencephalon of Dmrt3;Dmrt5 double KO embryos and downregulated when ventral telencephalic progenitors express ectopic Dmrt5. Conditional overexpression of Dmrt5 throughout the telencephalon produces gene expression and structural defects that are highly consistent with reduced GSX2 activity. Further, Emx2;Dmrt5 double KO embryos show a phenotype similar to Dmrt3;Dmrt5 double KO embryos, and both DMRT3, DMRT5 and the homeobox transcription factor EMX2 bind to a ventral telencephalon-specific enhancer in the Gsx2 locus. Together, our findings uncover cooperative functions of DMRT3, DMRT5, and EMX2 in dividing dorsal from ventral in the telencephalon. SIGNIFICANCE STATEMENT We identified the DMRT3 and DMRT5 zinc finger transcription factors as novel regulators of dorsoventral patterning in the telencephalon. Our data indicate that they have overlapping functions and compensate for one another. The double, but not the single, knock-out produces a dorsal telencephalon that is ventralized, and olfactory bulb tissue takes over most remaining cortex. Conversely, overexpressing Dmrt5 throughout the telencephalon causes expanded expression of dorsal gene determinants and smaller olfactory bulbs. Furthermore, we show that the homeobox transcription factor EMX2 that is coexpressed with DMRT3 and DMRT5 in cortical progenitors cooperates with them to maintain dorsoventral patterning in the telencephalon. Our study suggests that DMRT3/5 function with EMX2 in positioning the pallial-subpallial boundary by antagonizing the ventral homeobox transcription factor GSX2

    Cent scientifiques répliquent à SEA (Suppression des Expériences sur l’Animal vivant) et dénoncent sa désinformation

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    La lutte contre la maltraitance animale est sans conteste une cause moralement juste. Mais elle ne justifie en rien la désinformation à laquelle certaines associations qui s’en réclament ont recours pour remettre en question l’usage de l’expérimentation animale en recherche

    Neoproterozoic iron formation: An evaluation of its temporal, environmental and tectonic significance

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    Prdm12 in nociceptor development

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    In a recent study on individuals with Congenital Insensitivity to Pain (CIP), the Prdm12 gene has been identified as a novel gene causing painlessness that is required for the development of the nociceptors, the specialized neurons sensing tissue damage. Despite its importance in nociceptors, its exact function and mechanism of action remains elusive. Here we show that during mouse embryonic development, within the dorsal root ganglia that contains the cell bodies of the different types of sensory neurons, Prdm12 is selectively expressed in developing nociceptors and that in adults it remains expressed in mature nociceptors. Via the generation and characterization of null and conditional Prdm12 mutant lines, we demonstrate that Prdm12 is required in nociceptor progenitors for their survival, likely due to its requirement for the initiation of the expression of the neurotrophic receptor TrkA, and provide evidence that it is also essential in later maturing nociceptors for the expression of many pain-associated channels and receptors. Furthermore, using gain of function assays in pluripotent animal cap ectodermal explants, we show that Prdm12 promotes the ability of the proneural factor Neurogenin1 and 2 to induce TrkA expression and blocks their capacity to induce other sensory cell fates. Taken together, our findings point to Prdm12 as a critical regulator of nociceptor development and provide first explanation for its mechanism of action in sensory neurogenesis. Its role in mature nociceptive neurons and pain perception is currently studied assessing their electrophysiological properties and the behaviour responses of Prdm12 cKO mice to noxious stimuli.info:eu-repo/semantics/nonPublishe
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