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  • 1. Bratic, Ivana
    et al.
    Hench, Jürgen
    Södertörn University, School of Life Sciences.
    Henriksson, Johan
    Södertörn University, School of Life Sciences, Molecular biology.
    Antebi, Adam
    Bürglin, Thomas R.
    Trifunovic, Aleksandra
    Mitochondrial DNA level, but not active replicase, is essential for Caenorhabditis elegans development2009In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 37, no 6, p. 1817-1828Article in journal (Refereed)
    Abstract [en]

    A number of studies showed that the development and the lifespan of Caenorhabditis elegans is dependent on mitochondrial function. In this study, we addressed the role of mitochondrial DNA levels and mtDNA maintenance in development of C. elegans by analyzing deletion mutants for mitochondrial polymerase gamma (polg-1(ok1548)). Surprisingly, even though previous studies in other model organisms showed necessity of polymerase gamma for embryonic development, homozygous polg-1(ok1548) mutants had normal development and reached adulthood without any morphological defects. However, polg-1 deficient animals have a seriously compromised gonadal function as a result of severe mitochondrial depletion, leading to sterility and shortened lifespan. Our results indicate that the gonad is the primary site of mtDNA replication, whilst the mtDNA of adult somatic tissues mainly stems from the developing embryo. Furthermore, we show that the mtDNA copy number shows great plasticity as it can be almost tripled as a response to the environmental stimuli. Finally, we show that the mtDNA copy number is an essential limiting factor for the worm development and therefore, a number of mechanisms set to maintain mtDNA levels exist, ensuring a normal development of C. elegans even in the absence of the mitochondrial replicase.

  • 2.
    Hench, Jürgen
    et al.
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institutet.
    Henriksson, Johan
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Instiututet.
    Abou-Zied, Akram M
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institutet.
    Lüppert, Martin
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Instiutetet.
    Dethlefsen, Johan
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institutet.
    Mukherjee, Krishanu
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Intitutet.
    Tong, Yong Guang
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Intitutet.
    Tang, Lois
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institutet.
    Gangishetti, Umesh
    Karolinska Institutet.
    Baillie, David L
    Simon Fraser University, Burnaby, British Columbia, Canada.
    Bürglin, Thomas R
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institutet.
    The Homeobox Genes of Caenorhabditis elegans and Insights into Their Spatio-Temporal Expression Dynamics during Embryogenesis2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0126947Article in journal (Refereed)
    Abstract [en]

    Homeobox genes play crucial roles for the development of multicellular eukaryotes. We have generated a revised list of all homeobox genes for Caenorhabditis elegans and provide a nomenclature for the previously unnamed ones. We show that, out of 103 homeobox genes, 70 are co-orthologous to human homeobox genes. 14 are highly divergent, lacking an obvious ortholog even in other Caenorhabditis species. One of these homeobox genes encodes 12 homeodomains, while three other highly divergent homeobox genes encode a novel type of double homeodomain, termed HOCHOB. To understand how transcription factors regulate cell fate during development, precise spatio-temporal expression data need to be obtained. Using a new imaging framework that we developed, Endrov, we have generated spatio-temporal expression profiles during embryogenesis of over 60 homeobox genes, as well as a number of other developmental control genes using GFP reporters. We used dynamic feedback during recording to automatically adjust the camera exposure time in order to increase the dynamic range beyond the limitations of the camera. We have applied the new framework to examine homeobox gene expression patterns and provide an analysis of these patterns. The methods we developed to analyze and quantify expression data are not only suitable for C. elegans, but can be applied to other model systems or even to tissue culture systems.

  • 3.
    Hench, Jürgen
    et al.
    Södertörn University, School of Life Sciences.
    Henriksson, Johan
    Södertörn University, School of Life Sciences, Molecular biology.
    Lüppert, Martin
    Södertörn University, School of Life Sciences.
    Bürglin, Thomas R.
    Södertörn University, School of Life Sciences, Molecular biology.
    Spatio-temporal reference model of Caenorhabditis elegans embryogenesis with cell contact maps2009In: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 333, no 1, p. 1-13Article in journal (Refereed)
    Abstract [en]

    The nematode Caenorhabditis elegans has been used as a model for developmental biology for decades. Still, the few publicly available spatio-temporal (4D) data sets have conflicting information regarding variability of cell positions and are not well-suited for a standard 4D embryonic model, due to compression. We have recorded six uncompressed embryos, and determined their lineage and 4D coordinates, including nuclear radii, until the end of gastrulation. We find a remarkable degree of stability in the cell positions, as well as little rotational movement, which allowed us to combine the data into a single reference model of C. elegans embryogenesis. Using Voronoi decomposition we generated the list of all predicted cell contacts during early embryogenesis and calculated these contacts up to the similar to 150 cell stage, and find that about 1500 contacts last 2.5 min or longer. The cell contact map allows for comparison of multiple 4D data sets, e. g., mutants or related species, at the cellular level. A comparison of our uncompressed 4D model with a compressed embryo shows that up to 40% of the cell contacts can be different. To visualize the 4D model interactively we developed a software utility. Our model provides an anatomical resource and can serve as foundation to display 4D expression data, a basis for developmental systems biology.

  • 4.
    Henriksson, Johan
    et al.
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institute.
    Hench, Jürgen
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institute.
    Tong, Yong Guang
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institute.
    Johansson, Arvid
    Johansson, David
    Bürglin, Thomas R.
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institute.
    Endrov: an integrated platform for image analysis2013In: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 10, no 6, p. 454-456Article in journal (Refereed)
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