| 1. |
- Bourlat, Sarah, et al.
(författare)
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Feeding ecology of Xenoturbella bocki (phylum Xenoturbellida) revealed by genetic barcoding
- 2008
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Ingår i: Molecular Ecology Resources. - 1755-098X. ; 8, s. 18-22
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Tidskriftsartikel (refereegranskat)abstract
- The benthic marine worm Xenoturbella is frequently contaminated with molluscan DNA, which had earlier caused confusion resulting in a suggested bivalve relationship. In order to find the source of the contaminant, we have used molluscan sequences derived from Xenoturbella and compared them to barcodes obtained from several individuals of the nonmicroscopic molluscs sharing the same environment as Xenoturbella. Using cytochrome oxidase 1, we found the contaminating sequences to be 98% similar to the bivalve Ennucula tenuis. Using the highly variable D1-D2 region of the large ribosomal subunit in Xenoturbella, we found three distinct species of contaminating molluscs, one of which is 99% similar to the bivalve Abra nitida, one of the most abundant bivalves in the Gullmarsfjord where Xenoturbella was found, and another 99% similar to the bivalve Nucula sulcata. These data clearly show that Xenoturbella only contains molluscan DNA originating from bivalves living in the same environment, refuting former hypotheses of a bivalve relationship. In addition, these data suggest that Xenoturbella feeds specifically on bivalve prey from multiple species, possibly in the form of eggs and larvae.
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| 2. |
- Axäng, Claes, 1977, et al.
(författare)
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Developmental genetics of the C. elegans pharyngeal neurons NSML and NSMR.
- 2008
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Ingår i: BMC Developmental Biology. - 1471-213X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background We are interested in understanding how the twenty neurons of the C. elegans pharynx develop in an intricate yet reproducible way within the narrow confines of the embryonic pharyngeal primordium. To complement an earlier study of the pharyngeal M2 motorneurons, we have now examined the effect of almost forty mutations on the morphology of a bilateral pair of pharyngeal neurosecretory-motor neurons, the NSMs. Results A careful description of the NSM morphology led to the discovery of a third, hitherto unreported process originating from the NSM cell body and that is likely to play a proprioceptive function. We found that the three NSM processes are differently sensitive to mutations. The major dorsal branch was most sensitive to mutations that affect growth cone guidance and function (e.g. unc-6, unc-34, unc-73), while the major sub-ventral branch was more sensitive to mutations that affect components of the extracellular matrix (e.g. sdn-1). Of the tested mutations, only unc-101, which affects an adaptin, caused the loss of the newly described thin minor process. The major processes developed synaptic branches post-embryonically, and these exhibited activity-dependent plasticity. Conclusion By studying the effects of nearly forty different mutations we have learned that the different NSM processes require different genes for their proper guidance and use both growth cone dependent and growth cone independent mechanisms for establishing their proper trajectories. The two major NSM processes develop in a growth cone dependent manner, although the sub-ventral process relies more on substrate adhesion. The minor process also uses growth cones but uniquely develops using a mechanism that depends on the clathrin adaptor molecule UNC-101. Together with the guidance of the M2 neuron, this is the second case of a pharyngeal neuron establishing one of its processes using an unexpected mechanism.
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| 3. |
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| 4. |
- Astorga, Jeanette, 1976, et al.
(författare)
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Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4
- 2007
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Ingår i: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 134:20, s. 3753-61
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Tidskriftsartikel (refereegranskat)abstract
- The first vasculature of the developing vertebrate embryo forms by assembly of endothelial cells into simple tubes from clusters of mesodermal angioblasts. Maturation of this vasculature involves remodeling, pruning and investment with mural cells. Hedgehog proteins are part of the instructive endodermal signal that triggers the assembly of the first primitive vessels in the mesoderm. We used a combination of genetic and in vitro culture methods to investigate the role of hedgehogs and their targets in murine extraembryonic vasculogenesis. We show that Bmps, in particular Bmp4, are crucial for vascular tube formation, that Bmp4 expression in extraembryonic tissues requires the forkhead transcription factor Foxf1 and that the role of hedgehog proteins in this process is to activate Foxf1 expression in the mesoderm. We show in the allantois that genetic disruption of hedgehog signaling (Smo(-/-)) has no effect on Foxf1 expression, and neither Bmp4 expression nor vasculogenesis are disturbed. By contrast, targeted inactivation of Foxf1 leads to loss of allantoic Bmp4 and vasculature. In vitro, the avascular Foxf1(-/-) phenotype can be rescued by exogenous Bmp4, and vasculogenesis in wild-type tissue can be blocked by the Bmp antagonist noggin. Hedgehogs are required for activation of Foxf1, Bmp4 expression and vasculogenesis in the yolk sac. However, vasculogenesis in Smo(-/-) yolk sacs can be rescued by exogenous Bmp4, consistent with the notion that the role of hedgehog signaling in primary vascular tube formation is as an activator of Bmp4, via Foxf1.
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| 5. |
- Eriksson, Anders, 1975, et al.
(författare)
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Gene-history correlation and population structure.
- 2004
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Ingår i: Physical biology. - : IOP Publishing. - 1478-3967 .- 1478-3975. ; 1:3-4, s. 220-8
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Tidskriftsartikel (refereegranskat)abstract
- Correlation of gene histories in the human genome determines the patterns of genetic variation (haplotype structure) and is crucial to understanding genetic factors in common diseases. We derive closed analytical expressions for the correlation of gene histories in established demographic models for genetic evolution and show how to extend the analysis to more realistic (but more complicated) models of demographic structure. We identify two contributions to the correlation of gene histories in divergent populations: linkage disequilibrium, and differences in the demographic history of individuals in the sample. These two factors contribute to correlations at different length scales: the former at small, and the latter at large scales. We show that recent mixing events in divergent populations limit the range of correlations and compare our findings to empirical results on the correlation of gene histories in the human genome.
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| 6. |
- Jakobsen, J. S., et al.
(författare)
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Temporal ChIP-on-chip reveals Biniou as a universal regulator of the visceral muscle transcriptional network
- 2007
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Ingår i: Genes Dev. - : Cold Spring Harbor Laboratory. - 0890-9369. ; 21:19, s. 2448-60
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Tidskriftsartikel (refereegranskat)abstract
- Smooth muscle plays a prominent role in many fundamental processes and diseases, yet our understanding of the transcriptional network regulating its development is very limited. The FoxF transcription factors are essential for visceral smooth muscle development in diverse species, although their direct regulatory role remains elusive. We present a transcriptional map of Biniou (a FoxF transcription factor) and Bagpipe (an Nkx factor) activity, as a first step to deciphering the developmental program regulating Drosophila visceral muscle development. A time course of chromatin immunoprecipitatation followed by microarray analysis (ChIP-on-chip) experiments and expression profiling of mutant embryos reveal a dynamic map of in vivo bound enhancers and direct target genes. While Biniou is broadly expressed, it regulates enhancers driving temporally and spatially restricted expression. In vivo reporter assays indicate that the timing of Biniou binding is a key trigger for the time span of enhancer activity. Although bagpipe and biniou mutants phenocopy each other, their regulatory potential is quite different. This network architecture was not apparent from genetic studies, and highlights Biniou as a universal regulator in all visceral muscle, regardless of its developmental origin or subsequent function. The regulatory connection of a number of Biniou target genes is conserved in mice, suggesting an ancient wiring of this developmental program.
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| 7. |
- Mörck, Catarina, 1972, et al.
(författare)
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pha-2 encodes the C. elegans ortholog of the homeodomain protein HEX and is required for the formation of the pharyngeal isthmus.
- 2004
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Ingår i: Developmental Biology. - : Elsevier BV. - 0012-1606. ; 272:2, s. 403-418
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Tidskriftsartikel (refereegranskat)abstract
- The pha-2 mutant was isolated in 1993 by Leon Avery in a screen for worms with visible defects in pharyngeal feeding behavior. In pha-2 mutant worms, the pharyngeal isthmus is abnormally thick and short and, in contrast to wild-type worms, harbors several cell nuclei. We show here that pha-2 encodes a homeodomain protein and is homologous to the vertebrate homeobox gene, Hex (also known as Prh). Consistent with a function in pharyngeal development, the pha-2 gene is expressed in the pharyngeal primordium of Caenorhabditis elegans embryos, particularly in pm5 cells that form the bulk of the isthmus. We show that in the pha-2 mutant there is a failure of the pm5 cells to elongate anteriorly while keeping their nuclei within the nascent posterior bulb to form the isthmus during the 3-fold embryonic stage. We also present evidence that pha-2 regulates itself positively in pm5 cells, that it is a downstream target of the forkhead gene pha-4, and that it may also act in the isthmus as an inhibitor of the ceh-22 gene, an Nkx2.5 homolog. Finally, we have begun characterizing the regulation of the pha-2 gene and find that intronic sequences are essential for the complete pha-2 expression profile. The present report is the first to examine the expression and function of an invertebrate Hex homolog, that is, the C. elegans pha-2 gene.
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| 8. |
- Klevebring, Daniel, 1981-
(författare)
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On Transcriptome Sequencing
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is about the use of massive DNA sequencing to investigate the transcriptome. During recent decades, several studies have made it clear that the transcriptome comprises a more complex set of biochemical machinery than was previously believed. The majority of the genome can be expressed as transcripts; and overlapping and antisense transcription is widespread. New technologies for the interroga- tion of nucleic acids have made it possible to investigate such cellular phenomena in much greater detail than ever before. For each application, special requirements need to be met. The work presented in this thesis focuses on the transcrip- tome and the development of technology for its analysis. In paper I, we report our development of an automated approach for sample preparation. The procedure was benchmarked against a publicly available reference data set, and we note that our approach outperformed similar manual procedures in terms of reproducibility. In the work reported in papers II-IV, we used different massive sequencing technologies to investigate the transcriptome. In paper II we describe a concatemerization approach that increased throughput by 65% using 454 sequencing,and we identify classes of transcripts not previously described in Populus. Papers III and IV both report studies based on SOLiD sequencing. In the former, we investigated transcripts and proteins for 13% of the human gene and detected a massive overlap for the upper 50% transcriptional levels. In the work described in paper IV, we investigated transcription in non-genic regions of the genome and detected expression from a high number of previ- ously unknown loci.
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| 9. |
- Axäng, Claes, 1977, et al.
(författare)
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The twisted pharynx phenotype in C. elegans.
- 2007
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Ingår i: BMC Developmental Biology. - 1471-213X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background The pharynx of C. elegans is an epithelial tube whose development has been compared to that of the embryonic heart and the kidney and hence serves as an interesting model for organ development. Several C. elegans mutants have been reported to exhibit a twisted pharynx phenotype but no careful studies have been made to directly address this phenomenon. In this study, the twisting mutants dig-1, mig-4, mnm-4 and unc-61 are examined in detail and the nature of the twist is investigated. Results We find that the twisting phenotype worsens throughout larval development, that in most mutants the pharynx retains its twist when dissected away from the worm body, and that double mutants between mnm-4 and mutants with thickened pharyngeal domains (pha-2 and sma-1) have less twisting in these regions. We also describe the ultrastructure of pharyngeal tendinous organs that connect the pharyngeal basal lamina to that of the body wall, and show that these are pulled into a spiral orientation by twisted pharynges. Within twisted pharynges, actin filaments also show twisting and are longer than in controls. In a mini screen of adhesionmolecule mutants, we also identified one more twisting pharynx mutant, sax-7. Conclusion Defects in pharyngeal cytoskeleton length or its anchor points to the extracellular matrix are proposed as the actual source of the twisting force. The twisted pharynx is a useful and easy-to-score phenotype for genes required in extracellular adhesion or organ attachment, and perhaps forgenes required for cytoskeleton regulation.
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| 10. |
- Görnerup, Olof, 1977
(författare)
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Inference of Hierarchical Structure in Complex Systems
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hierarchical organization is a central property of complex systems. It is even argued that a system is required to be hierarchical in order to evolve complexity within reasonable time. A hierarchy of a system is defined as the set of self-contained levels at which the system operates and can be described on. Given a dynamical system there are only specific levels that are valid. This thesis mainly concerns the definition and inference of such levels. Paper I describes an algorithm for finding hierarchical levels in stochastic processes. The method systematically explores the set of possible partitions of a process' state space and statistically determines which of the partitions that impose closed dynamics. It is applicable to moderately sized systems. In Paper II an alternative approach that applies to linear dynamical systems is presented. In this case the spectral properties of the matrix that defines a system's dynamics is utilized, which allows for analysis of large systems (with on the order of thousand states). The specification and analysis of an algorithm that is based on the results in Paper II is presented in Paper III. Paper IV applies the spectral method and a complementary agglomeration method to infer aggregated dynamics in a Markov model of codon substitutions in DNA. The standard genetic code is identified as a projection that gives the hierarchical level of amino acid substitutions. Further, higher order amino acid groups that are relatively conserved under substitutions are found to define other levels of dynamics. Paper V and VI relate hierarchical organization to primordial evolution in a conceptual model that is based on the RNA world hypothesis. A well-stirred system of processes that catalyze the production of other processes is shown to successively build higher levels of organization from simple and general-purpose components by autocatalysis.
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