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  • Archer, Amena, et al. (författare)
  • Transcriptional activity and developmental expression of liver X receptor (lxr) in zebrafish
  • 2008
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 237:4, s. 1090-1098
  • Tidskriftsartikel (refereegranskat)abstract
    • Mammalian liver-X-receptors (LXRs) are transcription factors activated by oxysterols. They play an essential role in lipid and glucose metabolism. We have cloned the open reading frame of zebrafish lxr and describe its genomic organization. Zebrafish lxr encodes a 50-kDa protein with high sequence similarity to mammalian LXR alpha. In transfection assays, the encoded protein showed transcriptional activity in response to LXR-ligands. Treatment of adult zebrafish with the synthetic LXR ligand, GW3965, induced expression of genes involved in hepatic cholesterol and lipid pathways. Using qPCR and in situ hybridization, we found ubiquitous expression of lxr mRNA during the first 24 hr of development, followed by more restricted expression, particularly to the liver at 3dpf and the liver and intestine at 4dpf. In adult fish, all examined organs expressed lxr. In addition to a metabolic role of lxr, the temporal expression pattern suggests a developmental role in, e.g., the liver and CNS.
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  • Blixt, Maria K. E., et al. (författare)
  • Zinc finger gene nolz1 regulates the formation of retinal progenitor cells and suppresses the Lim3/Lhx3 phenotype of retinal bipolar cells in chicken retina
  • 2018
  • Ingår i: Developmental Dynamics. - : WILEY. - 1058-8388 .- 1097-0177. ; 247:4, s. 630-641
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The zinc-finger transcription factor Nolz1 regulates spinal cord neuron development by interacting with the transcription factors Isl1, Lim1, and Lim3, which are also important for photoreceptors, horizontal and bipolar cells during retinal development. We, therefore, studied Nolz1 during retinal development.Results: Nolz1 expression was seen in two waves during development: one early (peak at embryonic day 3-4.5) in retinal progenitors and one late (embryonic day 8) in newly differentiated cells in the inner nuclear layer. Overexpression and knockdown showed that Nolz1 decreases proliferation and stimulates cell cycle withdrawal in retinal progenitors with effects on the generation of retinal ganglion cells, photoreceptors, and horizontal cells without triggering apoptosis. Overexpression of Nolz1 gave more p27 positive cells. Sustained overexpression of Nolz1 in the retina gave fewer Lim3/Lhx3 bipolar cells.Conclusions: We conclude that Nolz1 has multiple functions during development and suggest a mechanism in which Nolz1 initially regulates the proliferation state of the retinal progenitor cells and then acts as a repressor that suppresses the Lim3/Lhx3 bipolar cell phenotype at the time of bipolar cell differentiation.
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  • Boije, Henrik, et al. (författare)
  • Pax2 Is Expressed in a Subpopulation of Muller Cells in the Central Chick Retina
  • 2010
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 239:6, s. 1858-1866
  • Tidskriftsartikel (refereegranskat)abstract
    • Muller cells in the chick retina are generally thought to be a homogeneous population. We show that the transcription factor Pax2 is expressed by Muller cells in the central chick retina and its expression was first observed at stage 32 (embryonic day [E] 7.5). Birth-dating indicated that the majority of Pax2-positive Muller cells are generated between stage 29 and 33 (E5.5-E8). At stage 42 (E16), several Muller cell markers, such as Sox2 and 2M6, had reached the peripheral retina, while the Pax2 labeling extended approximately half-way. A similar pattern was maintained in the 6-month-old chicken. Neither the Pax2-positive nor the Pax2-negative Muller cells could be specifically associated to proliferative responses in the retina induced by growth factors or N-methyl-D-aspartate. Pax2 was not detected in Muller cells in mouse, rat, guinea-pig, rabbit, or pig retinas; but the zebrafish retina displayed a similar pattern of central Pax2-expressing Muller cells.
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  • Boström, Hans, et al. (författare)
  • PDGF-A/PDGF alpha-receptor signaling is required for lung growth and the formation of alveoli but not for early lung branching morphogenesis
  • 2002
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 223:1, s. 155-162
  • Tidskriftsartikel (refereegranskat)abstract
    • Platelet-derived growth factors (PDGF) constitute a family of four gene products (PDGF-A-D) acting by means of two receptor tyrosine kinases, PDGFR alpha and beta. Three of the ligands (PDGF-A, -B, and -C) bind to PDGFR alpha with high affinity. Knockout of pdgf-a in mice has demonstrated a role for PDGF-A in the recruitment of smooth muscle cells to the alveolar sacs and their further compartmentalization into alveoli. Although this is a late, postnatal step in lung development, pdgf-a antisense oligonucleotides were previously shown to inhibit epithelial branching in rat lung explants in vitro, which reflects an early embryonic process. These conflicting results may be explained by substitution of genetic loss of pdgf-a by maternal transfer of PDGF-A to the knockout embryo or the presence of other PDGFR alpha agonists (PDGF-B and -C) in vivo, potentially masking an effect of PDGF-A on branching morphogenesis. Alternatively, the administration of pdgf-a antisense oligonucleotides affected other processes than the intended. To discriminate between these opposing possibilities, we have analyzed lung development in pdgfr alpha -/- embryos and lung primordia grown in vitro. Our analysis shows that, while the pdgfr alpha -/- lungs and explanted lung rudiments were smaller than normal, branching morphogenesis appears qualitatively intact and proceeds until at least embryonic day 15.5, generating both prospective conducting and respiratory airways. We conclude that, although PDGF-AA signaling over PDGFR alpha may have direct or indirect roles in overall lung growth, it does not specifically control early branching of the lung epithelium.
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  • Burguière, Anne-Cecile, 1980-, et al. (författare)
  • Alkali-like myosin light chain-1 (myl1) is an early marker for differentiating fast muscle cells in zebrafish
  • 2011
  • Ingår i: Developmental Dynamics. - : John Wiley & Sons. - 1058-8388 .- 1097-0177. ; 240:7, s. 1856-1863
  • Tidskriftsartikel (refereegranskat)abstract
    • During myogenesis, muscle precursors become divided into either fast- or slow-twitch fibres, which in the zebrafish occupy distinct domains in the embryo. Genes encoding sarcomeric proteins specific for fast or slow fibres are frequently used as lineage markers. In an attempt to identify and evaluate early definitive markers for cells in the fast-twitch pathway, we analysed genes encoding proteins contributing to the fast sarcomeric structures. The previously uncharacterized zebrafish alkali-like myosin light chain gene (myl1) was found to be expressed exclusively in cells in the fast-twitch pathway initiated at an early stage of fast fibre differentiation. Myl1 was expressed earlier, and in a more fibre type restricted manner, than any of the previously described and frequently used fast myosin light and heavy chain and troponin muscle markers mylz2, mylz3, tnni2, tnnt3a, fMyHC1.3. In summary, this study introduces a novel marker for early differentiating fast muscle cells.
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  • Chen, Shoujun, et al. (författare)
  • Fibromodulin Regulates Collagen Fibrillogenesis During Peripheral Corneal Development
  • 2010
  • Ingår i: Developmental Dynamics. - : Wiley. - 1097-0177 .- 1058-8388. ; 239:3, s. 844-854
  • Tidskriftsartikel (refereegranskat)abstract
    • Fibromodulin regulates collagen fibrillogenesis, but its existence/role(s) in the cornea is controversial. We hypothesize that fibromodulin regulates fibrillogenesis during postnatal development of the anterior eye. Fibromodulin is weakly expressed in the limbus at post-natal day (P) 4, increases and extends into the central cornea at P14, becomes restricted to the limbus at P30, and decreases at P60. This differential spatial and temporal expression of fibromodulin is coordinated with emmetropization; the developmental increase in axial length and globe size. Genetic analysis demonstrated that fibromodulin regulates fibrillogenesis in a region-specific manner. At the limbus, fibromodulin is dominant in regulating fibril growth during postnatal development. In the posterior peripheral cornea, cooperative interactions of fibromodulin and lumican regulate fibrillogenesis. These data indicate that fibromodulin plays important roles in the regulation of region-specific fibrillogenesis required for the integration of the corneal and scleral matrices and sulcus development required for establishment of the visual axis. Developmental Dynamics 239:844-854, 2010 (C) 2010 Wiley-Liss, Inc.
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13.
  • Eaton, Jennifer L., et al. (författare)
  • Ontogeny of vasotocin-expressing cells in zebrafish: Selective requirement for the transcriptional regulators orthopedia and single-minded 1 in the preoptic area
  • 2008
  • Ingår i: Developmental Dynamics. - : Wiley. - 1097-0177 .- 1058-8388. ; 237:4, s. 995-1005
  • Tidskriftsartikel (refereegranskat)abstract
    • The neurohypophysial peptide arginine vasotocin, and its mammalian ortholog arginine vasopressin, influence a wide range of physiological and behavioral responses, including aspects of sexual and social behaviors, osmoregulation, stress response, metabolism, blood pressure, and circadian rhythms. Here, we demonstrate that, in zebrafish (Danio rerio), the vasotocin precursor gene arginine vasotocin-neurophysin (avt) is expressed in two domains in the developing embryo: the dorsal preoptic area and the ventral hypothalamus. In the dorsal preoptic area, avt-expressing cells are intermingled with isotocin-neurophysin (ist) -expressing cells, and these neurons project to the neurohypophysis (posterior pituitary). In the dorsal preoptic area, the transcriptional regulators orthopedia b (otpb) and simple-minded 1 (siml) are required for expression of both avt and ist. In contrast, olp and siml are not required for avt expression in the ventral hypothalamus. Thus, the development of these two avt expression domains is influenced by separate gene regulatory networks.
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  • Fagman, Henrik, 1975, et al. (författare)
  • The developing mouse thyroid: embryonic vessel contacts and parenchymal growth pattern during specification, budding, migration, and lobulation.
  • 2006
  • Ingår i: Developmental dynamics : an official publication of the American Association of Anatomists. - : Wiley. - 1058-8388. ; 235:2, s. 444-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Normal mouse thyroid development has been revised to identify critical morphogenetic events. The early thyroid primordium associates with the aortic sac endothelium at the time of specification and budding. The vascular contact is lost after the thyroid buds from the pharyngeal endoderm, but is resumed before the gland divides to form two lobes. Lateral expansion of parenchyma takes place along the course of the third pharyngeal arch arteries. Thyroid precursor cells expressing Titf1/Nkx2.1 do not proliferate until the migration stage, implicating that progenitors likely are recruited from outside the thyroid placode. Early lobulation involves engulfment of the entire ultimobranchial bodies by the growing midline thyroid. At the same time, proliferation of the ultimobranchial body epithelium is silenced preceding the differentiation of C cells. Before folliculogenesis, thyroid lobe enlargement is reminiscent of a budding-branching-like growth pattern. It is suggested that thyroid inductive signals arise from embryonic vessels, and that this provides ideas to conceptually new pathogenetic mechanisms of thyroid dysgenesis.
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  • Filipek-Gorniok, Beata, et al. (författare)
  • Expression of chondroitin/dermatan sulfate glycosyltransferases during early zebrafish development
  • 2013
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 242:8, s. 964-975
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chondroitin/dermatan sulfate (CS/DS) proteoglycans present in the extracellular matrix have important structural and regulatory functions. Results: Six human genes have previously been shown to catalyze CS/DS polymerization. Here we show that one of these genes, chpf, is represented by two copies in the zebrafish genome, chpfa and chpfb, while the other five human CS/DS glycosyltransferases csgalnact1, csgalnact2, chpf2, chsy1, and chsy3 all have single zebrafish orthologues. The putative zebrafish CS/DS glycosyltransferases are spatially and temporally expressed. Interestingly, overlapping expression of multiple glycosyltransferases coincides with high CS/DS deposition. Finally, whereas the relative levels of the related polysaccharide HS reach steady-state at around 2 days post fertilization, there is a continued relative increase of the CS amounts per larvae during the first 6 days of development, matching the increased cartilage formation. Conclusions: There are 7 CS/DS glycosyltransferases in zebrafish, which, based on homology, can be divided into the CSGALNACT, CHSY, and CHPF families. The overlap between intense CS/DS production and the expression of multiple CS/DS glycosyltransferases suggests that efficient CS/DS biosynthesis requires a combination of several glycosyltransferases.
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  • Fried, K., et al. (författare)
  • Expression of ErbB3, ErbB4, and neuregulin-1 mRNA during tooth development
  • 2002
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 224:3, s. 356-360
  • Tidskriftsartikel (refereegranskat)abstract
    • The receptor tyrosine kinases ErbB3 and ErbB4, which bind to various variants of neuregulin (NRG), play fundamental roles in neural development and in organs, which form through epithelial-mesenchymal interactions. Here, we demonstrate that NRG-1 and the receptors ErbB3 and ErbB4 are expressed locally during rodent tooth development. However, the mRNA expression patterns of ErbB3 and ErbB4 were distinctly different during odontogenesis. Examinations of teeth in genetically heart-rescued ErbB4-/- mice did not reveal any obvious deviation from the normal phenotype. The results suggest that ErbB3 and ErbB4 may participate in tooth morphogenesis. The specific interactions between NRG isoforms and ErbB receptors during this process remain to be determined.
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  • Hao, Limin, et al. (författare)
  • The hedgehog-related gene qua-1 is required for molting in Caenorhabditis elegans
  • 2006
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 235:6, s. 1469-1481
  • Tidskriftsartikel (refereegranskat)abstract
    • The Caenorhabditis elegans genome encodes ten proteins that share similarity with Hedgehog through the C-terminal Hint/Hog domain. While most genes are members of larger gene families, qua-1 is a single copy gene. Here we show that orthologs of qua-1 exist in many nematodes, including Brugia malayi, which shared a common ancestor with C. elegans about 300 million years ago. The QUA-1 proteins contain an N-terminal domain, the Qua domain, that is highly conserved, but whose molecular function is not known. We have studied the expression pattern of qua-1 in C. elegans using a qua-1::GFP transcriptional fusion. qua-1 is mainly expressed in hyp1 to hyp11 hypodermal cells, but not in seam cells. It is also expressed in intestinal and rectal cells, sensilla support cells, and the P cell lineage in L1. The expression of qua-1::GFP undergoes cyclical changes during development in phase with the molting cycle. It accumulates prior to molting and disappears between molts. Disruption of the qua-1 gene function through an internal deletion that causes a frame shift with premature stop in the middle of the gene results in strong lethality. The animals arrest in the early larval stages due to defects in molting. Electron microscopy reveals double cuticles due to defective ecdysis, but no obvious defects are seen in the hypodermis. Qua domain-only::GFP and full-length QUA-1::GFP fusion constructs are secreted and associated with the overlying cuticle, but only QUA-1::GFP rescues the mutant phenotype. Our results suggest that both the Hint/Hog domain and Qua domain are critically required for the function of QUA-1.
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  • Hart, Alan, et al. (författare)
  • Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells.
  • 2003
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 228:2, s. 185-193
  • Tidskriftsartikel (refereegranskat)abstract
    • The pancreas is an endodermally derived organ that initially appears as a dorsal and ventral protrusion of the primitive gut epithelium. The pancreatic progenitor cells present in these early pancreatic anlagen proliferate and eventually give rise to all pancreatic cell types. The fibroblast growth factor receptor (FGFR) 2b high-affinity ligand FGF10 has been linked to pancreatic epithelial cell proliferation, and we have shown previously that Notch signalling controls pancreatic cell differentiation by means of lateral inhibition. In the developing pancreas, activated intracellular Notch appears to be required for maintaining cells in the progenitor state, in part by blocking the expression of the pro-endocrine gene neurogenin 3 (ngn3), and hence endocrine cell differentiation. Here, we show that persistent expression of Fgf10 in the embryonic pancreas of transgenic mice also inhibits pancreatic cell differentiation, while stimulating pancreatic epithelial cell proliferation. We provide evidence that one of the effects of the persistent expression of Fgf10 in the developing pancreas is maintained Notch activation, which results in impaired expression of ngn3 within the pancreatic epithelium. Together, our data suggest a role for FGF10/FGFR2b signalling in regulation of pancreatic cell proliferation and differentiation and that FGF10/FGFR2b signalling affects the Notch-mediated lateral inhibition pathway.
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  • Janssen, Ralf, 1975-, et al. (författare)
  • Expression of netrin and its receptors uncoordinated-5 and frazzled in arthropods and onychophorans suggests conserved and diverged functions in neuronal pathfinding and synaptogenesis
  • 2023
  • Ingår i: Developmental Dynamics. - : John Wiley & Sons. - 1058-8388 .- 1097-0177. ; 252:1, s. 172-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Development of the nervous system and the correct connection of nerve cells require coordinated axonal pathfinding through an extracellular matrix. Outgrowing axons exhibit directional growth toward or away from external guidance cues such as Netrin. Guidance cues can be detected by growth cones that are located at the end of growing axons through membrane-bound receptors such as Uncoordianted-5 and Frazzled. Binding of Netrin causes reformation of the cytoskeleton and growth of the axon toward (or away from) the source of Netrin production. Results Here, we investigate the embryonic mRNA expression patterns of netrin genes and their potential receptors, uncoordinated-5 and frazzled in arthropod species that cover all main branches of Arthropoda, that is, Pancrustacea, Myriapoda, and Chelicerata. We also studied the expression patterns in a closely related outgroup species, the onychophoran Euperipatoides kanangrensis, and provide data on expression profiles of these genes in larval tissues of the fly Drosophila melanogaster including the brain and the imaginal disks. Conclusion Our data reveal conserved and diverged aspects of neuronal guidance in Drosophila with respect to the other investigated species and suggest a conserved function in nervous system patterning of the developing appendages.
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24.
  • Jaskoll, T., et al. (författare)
  • Sonic hedgehog signaling plays an essential role during embryonic salivary gland epithelial branching morphogenesis
  • 2004
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 229:4, s. 722-732
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene targeting studies indicate that sonic hedgehog (Shh) signaling plays an essential role during craniofacial development. Because numerous mandibular derivatives (e.g., teeth, tongue, Meckel's cartilage) are absent in Shh null mice and the embryonic submandibular salivary gland (SMG) develops from the mandibular arch, we postulated that Shh signaling is important for embryonic SMG development. To address this question, we first determined the spatiotemporal distribution of Shh; two transmembrane proteins, patched 1 (Ptc) and Smoothened (Smo), which act as a negative or a positive regulator of the Shh signal, respectively; and the Gli 3 transcription factor, which is downstream of the Shh signal. The epithelial localization of Shh, Ptc, Smo, and Gli 3 suggests that Shh signaling may act within the epithelium in a juxtacrine manner. The SMG phenotype in our embryonic day (E) 18.5 Shh null mice can be characterized as "paedomorphic," that is, it fails to progress to ontogenic stages beyond the Early Pseudoglandular (similar toE14). In a complementary set of experiments, we used organ culture to evaluate the effect of enhanced or abrogated Shh signaling on embryonic SMG development in vitro. Paired Ell 3 (Late Initial Bud stage) or E14 (Pseudogiandular stage) SMGs were cultured in the presence or absence of exogenous Shh peptide supplementation; Shh-supplemented explants exhibit a significant stage-dependent increase in branching morphogenesis compared with control explants. Furthermore, by using cyclopamine, a steroidal alkaloid that specifically disrupts the Shh pathway, to abrogate endogenous Shh signaling in vitro, we found a significant decrease in branching in cyclopamine-treated explants compared with controls, as well as a significant decrease in epithelial cell proliferation. Our results indicate that Shh signaling plays an essential role during embryonic SMG branching morphogenesis. Exogenous FGF8 peptide supplementation in vitro, rescues the abnormal SMG phenotype seen in cyclopamine-treated explants, demonstrating that overexpression of a parallel, but related, downstream signaling pathway can compensate for diminished Shh signaling and restore embryonic SMG branching morphogenesis. (C) 2004 Wiley-Liss, Inc.
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  • Jolly, Mohit Kumar, et al. (författare)
  • Epithelial–mesenchymal transition, a spectrum of states : Role in lung development, homeostasis, and disease
  • 2018
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388. ; 247:3, s. 346-358
  • Forskningsöversikt (refereegranskat)abstract
    • Epithelial–mesenchymal transition (EMT) plays key roles during lung development and many lung diseases such as chronic obstructive pulmonary disease (COPD), lung cancer, and pulmonary fibrosis. Here, integrating morphological observations with underlying molecular mechanisms, we highlight the functional role of EMT in lung development and injury repair, and discuss how it can contribute to pathogenesis of chronic lung disease. We discuss the evidence of manifestation of EMT and its potential driving role in COPD, idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans syndrome (BOS), and lung cancer, while noting that all cells need not display a full EMT in any of these contexts, i.e., often cells co-express epithelial and mesenchymal markers but do not fully convert to extracellular matrix (ECM) -producing fibroblasts. Finally, we discuss recent therapeutic attempts to restrict EMT in chronic lung disease. Developmental Dynamics 247:346–358, 2018.
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26.
  • Jones, Iwan, et al. (författare)
  • Reduced mTORC1-signaling in retinal ganglion cells leads to vascular retinopathy
  • 2022
  • Ingår i: Developmental Dynamics. - : John Wiley & Sons. - 1058-8388 .- 1097-0177. ; 251:2, s. 321-335
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The coordinated wiring of neurons, glia and endothelial cells into neurovascular units is critical for central nervous system development. This is best exemplified in the mammalian retina where interneurons, astrocytes and retinal ganglion cells sculpt their vascular environment to meet the metabolic demands of visual function. Identifying the molecular networks that underlie neurovascular unit formation is an important step towards a deeper understanding of nervous system development and function.Results: Here, we report that cell-to-cell mTORC1-signaling is essential for neurovascular unit formation during mouse retinal development. Using a conditional knockout approach we demonstrate that reduced mTORC1 activity in asymmetrically positioned retinal ganglion cells induces a delay in postnatal vascular network formation in addition to the production of rudimentary and tortuous vessel networks in adult animals. The severity of this vascular phenotype is directly correlated to the degree of mTORC1 down regulation within the neighboring retinal ganglion cell population.Conclusions: This study establishes a cell nonautonomous role for mTORC1-signaling during retinal development. These findings contribute to our current understanding of neurovascular unit formation and demonstrate how ganglion cells actively sculpt their local environment to ensure that the retina is perfused with an appropriate supply of oxygen and nutrients.
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27.
  • Kitambi, Satish S., et al. (författare)
  • Spatiotemporal Features of Neurogenesis in the Retina of Medaka, Oryzias latipes
  • 2008
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 237:12, s. 3870-3881
  • Tidskriftsartikel (refereegranskat)abstract
    • The vertebrate retina is very well conserved in evolution. Its structure and functional features are very similar in phyla as different as primates and teleost fish. Here, we describe the spatiotemporal characteristics of neurogenesis in the retina of a teleost, medaka, and compare them with other species, primarily the zebrafish. Several intriguing differences are observed between medaka and zebrafish. For example, photoreceptor differentiation in the medaka retina starts independently in two different areas, and at more advanced stages of differentiation, medaka and zebrafish retinae display obviously different patterns of the photoreceptor cell mosaic. Medaka and zebrafish evolutionary lineages are thought to have separated from each other 110 million years ago, and so the differences between these species are not unexpected, and may be exploited to gain insight into the architecture of developmental pathways. Importantly, this work highlights the benefits of using multiple teleost models in parallel to understand a developmental process.
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28.
  • Kriz, Vitezslav, et al. (författare)
  • Shb null allele is inherited with a transmission ratio distortion and causes reduced viability in utero
  • 2007
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 236:9, s. 2485-2492
  • Tidskriftsartikel (refereegranskat)abstract
    • SHB is an Src homology 2 domain-containing adapter protein that has been found to be involved in numerous cellular responses. We have generated an Shb knockout mouse. No Shb-/- pups or embryos were obtained on the C57Bl6 background, indicating an early defect as a consequence of Shb- gene inactivation on this genetic background. Breeding heterozygotes for Shb gene inactivation (Shb+/-) on a mixed genetic background (FVB/C57Bl6/129Sv) reveals a distorted transmission ratio of the null allele with reduced numbers of Shb+/+ and Shb-/- animals, but increased number of Shb+/- animals. The Shb- allele is associated with various forms of malformations, explaining the relative reduction in the number of Shb-/- offspring. Shb-/- animals that were born were viable, fertile, and showed no obvious defects. However, Shb+/- female mice ovulated preferentially Shb- oocytes explaining the reduced frequency of Shb+/+ mice. Our study suggests a role of SHB during reproduction and development.
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29.
  • Kropp, Marlene, et al. (författare)
  • The expression profile of the tumor suppressor gene Lzts1 suggests a role in neuronal development
  • 2012
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 241:5, s. 984-994
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neuronal circuit assembly comprises a number of developmental processes that ultimately underlie function. Identifying the molecular events that dictate these processes can give key insights into how neuronal circuit formation is coordinated. To begin to identify such molecular mechanisms, we have analysed the expression of a candidate gene of entirely unknown function within the nervous system. Here we reveal the spatial and temporal distribution of Lzts1 in mouse and chick embryonic spinal cord and propose potential biological functions. Results: Lzts1 mRNA is transiently expressed at the border of the ventricular and mantle zones in subsets of sensory and motor spinal neurons. The protein is localized to the cell body, axon, and trailing process of motor, commissural, and dorsal root neurons during development. Conclusions: Taken together, the spatial and temporal distribution of Lzts1 is consistent with a potential function(s) in cell cycle regulation, axon growth or guidance, and/or migration of neurons. Developmental Dynamics 241:984994, 2012. (c) 2012 Wiley Periodicals, Inc.
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31.
  • Landgren, Henrik, 1978, et al. (författare)
  • FoxJ3, a novel mammalian forkhead gene expressed in neuroectoderm, neural crest, and myotome
  • 2004
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 231:2, s. 396-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Forkhead transcription factors are important regulators of animal development. Here, we describe the embryonic expression pattern for one of the novel forkhead genes that were discovered as a result of the mouse and human genome projects. It is most closely related to FoxJ2 and has been assigned the name FoxJ3. The 100-kb, 13-exon mouse Foxj3 gene on chromosome 4 encodes a 623 amino acid (aa) protein from an mRNA of at least 4.8 kb (Human FOXJ3: Chr 1, 627 aa, 5.3-kb mRNA). During the stages of mouse development investigated (embryonic day [E] 8.5-E12.5) Foxj3 is expressed in neuroectoderm, in neural crest, and in many structures derived from neural crest cells, such as facioacoustic, trigeminal, and dorsal root ganglia. Stripes of expression appear at E10.5 in the location of myotomes and expand ventrally in a pattern similar to the developing body wall musculature. Developing limbs have a complex pattern of Foxj3 expression that at E12.5 colocalizes with the condensed mesenchyme of the skeletal primordia. (C) 2004 Wiley-Liss, Inc.
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32.
  • Lara-Ramirez, Ricardo, et al. (författare)
  • Characterization of two neurogenin genes from the brook lamprey lampetra planeri and their expression in the lamprey nervous system
  • 2015
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 244:9, s. 1096-1108
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neurogenins are required for the specification of neuronal precursors and regulate the expression of basic Helix-Loop-Helix genes involved in neuronal differentiation. Jawed vertebrates possess three Neurogenin paralogy groups and their combined expression covers the entire nervous system, apart from the autonomic nervous system. Results: Here we report the isolation of two Neurogenin genes, LpNgnA and LpNgnB, from the lamprey Lampetra planeri. Phylogenetic analyses show both genes have orthologues in other lamprey species and in a hagfish. Neither gene shows evidence of orthology to specific jawed vertebrate Neurogenin paralogues. LpNgnA is expressed in the ventricular zone of regions of the brain and spinal cord, with expression in the brain demarcating brain sub-compartments including the pallium, tegmentum, tectum, and dorsal thalamus. In the peripheral nervous system, LpNgnA is expressed in cranial sensory placodes and their derivatives, and in the dorsal root ganglia. LpNgnB is expressed transiently in placodal head ectoderm and throughout the central nervous system in early development, and in a small population cells that form part of the macula. Conclusions: Combined, LpNgnA and LpNgnB were detected in most cell populations marked by Neurogenin gene expression in jawed vertebrates, with the exception of the cerebellum, retina and the non-neural expression sites. (c) 2015 Wiley Periodicals, Inc.
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33.
  • Leigh, Nicholas D, et al. (författare)
  • Rebuilding limbs, one cell at a time
  • 2022
  • Ingår i: Developmental Dynamics. - : Wiley. - 1097-0177 .- 1058-8388. ; 251:9, s. 1389-1403
  • Tidskriftsartikel (refereegranskat)abstract
    • The regeneration of salamander limbs has been a special fascination among scientists and keen observers for centuries. Perhaps due to how closely the salamander's limb anatomically mirrors our own, a grand aspiration of regenerative medicine has been to provoke such a process following injury or loss of human limbs. Research in the last century has focused on understanding the blastema, a proliferative cell mass that develops after limb amputation (see Box 1 “A primer on limb regeneration” and reviews for discussion of foundational knowledge1-3). The first micrographs of limb blastemas (examples in Thornton4 and Hay5) brought limb regeneration to a cellular level and ushered in a new era of questions centered around the origin, potency, and processes of regenerative cells that has occupied the field ever since. Within this commentary, we will outline some of these persistent questions underlying limb regeneration, and how new technologies and approaches are paving the way toward a cellular understanding of complex tissue regeneration.
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34.
  • Lopes, SMCDS, et al. (författare)
  • Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction
  • 2004
  • Ingår i: Developmental Dynamics. - : Wiley. - 1097-0177 .- 1058-8388. ; 231:3, s. 542-550
  • Tidskriftsartikel (refereegranskat)abstract
    • Connective tissue growth factor (CTGF) is reported to be a target gene of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) in vitro. Its physiological role in angiogenesis and skeletogenesis during mouse development has been described recently. Here, we have mapped expression of CTGF mRNA during mouse heart development, postnatal adult life, and after experimental myocardial infarction. Furthermore, we investigated the relationship between CTGF and the BMP/TGFbeta signaling pathway in particular during heart development in mutant mice. Postnatally, CTGF expression in the heart became restricted to the atrium. Strikingly, 1 week after myocardial infarction, when myocytes have disappeared from the infarct zone, CTGF and TGFbeta expression as well as activated forms of TGFbeta but not BMP, Smad effector proteins are colocalized exclusively in the fibroblasts of the scar tissue, suggesting possible cooperation between CTGF and TGFbeta, during the pathological fibrotic response. (C) 2004 Wiley-Liss, Inc.
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35.
  • Maier, Esther, et al. (författare)
  • Dynamic expression of neurogenic markers in the developing chick olfactory epithelium
  • 2009
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 238:6, s. 1617-1625
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurogenesis in the olfactory epithelium begins in early embryos and proceeds throughout life. A comparison of neurogenic marker expression at different developmental stages and at different axes of the olfactory epithelium has not been reported in a coordinated way. In this study, we have in detail compared the temporal and spatial expression patterns of the precursor markers Hes5, Cash1, Ngn1, and the neuronal markers Gap43, HuC/D, Lhx2 in the developing olfactory placode and epithelium in chick embryos from HH10 to HH34. We show that Hes5 starts to be expressed in cells of the prospective olfactory placode at HH10, earlier then previously reported. During olfactory pit stages, the expression of Hes5, Cash1, Ngn1, Gap43, HuC/D, and Lhx2 varies throughout the anterior-posterior and superior-inferior axis of the olfactory epithelium. By HH34, expression of the precursor and neuronal markers show the first signs of apical-basal stratification of the epithelium. Developmental Dynamics 238:1617-1625, 2009. (c) 2009 Wiley-Liss, Inc.
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36.
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37.
  • Mellenthin, Katja, et al. (författare)
  • Wingless signaling in a large insect, the blowfly Lucilia sericata: A beautiful example of evolutionary developmental biology
  • 2006
  • Ingår i: Developmental Dynamics. - : Wiley. - 1097-0177 .- 1058-8388. ; 235:2, s. 347-360
  • Tidskriftsartikel (refereegranskat)abstract
    • Blowflies are the primary facultative agent in causing myiasis of domestic sheep in the whole world and, at the same time, it is an important tool for forensic medicine. Surprisingly, and in contrast to its importance, almost no data regarding the embryology and molecular markers are known for this insect. In this report, we present a detailed description of the blowfly Lucilia sericata embryogenesis and of imaginal disc development. The embryogenesis of Lucilia strongly resembles that of Drosophila, despite their apparent size difference. Moreover, imaginal disc development appears to be equally well conserved. Through cloning, expression, and functional studies, we show that the Lucilia Wingless (Wg) protein is highly conserved between the two species. We further show that parasegments are established in Lucilia, however, engrailed expression shows a more dynamic expression pattern than expected in comparison to Drosophila. Over-expression of Lucilia Wingless in Drosophila shows wingless-like wing phenotypes, suggesting that Lucilia Wingless blocks the signalling activity of Drosophila Wingless. Upon injection of wg dsRNA, we observe a "lawn of denticle" phenotype, closely resembling that of Drosophila. Due to the large size of the insect, the distance over which Wingless exerts signalling activity is up to three times larger than in Drosophila, yet the consequences are very similar. Our data demonstrate long-range wingless signaling mechanisms adapted for patterning large domains of naked cuticle and suggest signaling properties of Lucilia Wingless that are distinct from those of Drosophila Wingless.
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38.
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39.
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40.
  • Niklasson, Camilla U., et al. (författare)
  • Hypoxia inducible factor-2 alpha importance for migration, proliferation, and self-renewal of trunk neural crest cells
  • 2021
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 250:2, s. 191-236
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The neural crest is a transient embryonic stem cell population. Hypoxia inducible factor (HIF)-2 α is associated with neural crest stem cell appearance and aggressiveness in tumors. However, little is known about its role in normal neural crest development.Results: Here, we show that HIF-2 α is expressed in trunk neural crest cells of human, murine, and avian embryos. Knockdown as well as overexpression of HIF-2 α in vivo causes developmental delays, induces proliferation, and self-renewal capacity of neural crest cells while decreasing the proportion of neural crest cells that migrate ventrally to sympathoadrenal sites. Reflecting the in vivo phenotype, transcriptome changes after loss of HIF-2 α reveal enrichment of genes associated with cancer, invasion, epithelial-to-mesenchymal transition, and growth arrest.Conclusions: Taken together, these results suggest that expression levels of HIF-2 α must be strictly controlled during normal trunk neural crest development and that dysregulated levels affects several important features connected to stemness, migration, and development.
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41.
  • Nord, Christoffer, et al. (författare)
  • Reduced mTORC1-signaling in progenitor cells leads to retinal lamination deficits
  • 2024
  • Ingår i: Developmental Dynamics. - : John Wiley & Sons. - 1058-8388 .- 1097-0177.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neuronal lamination is a hallmark of the mammalian central nervous system (CNS) and underlies connectivity and function. Initial formation of this tissue architecture involves the integration of various signaling pathways that regulate the differentiation and migration of neural progenitor cells.Results: Here, we demonstrate that mTORC1 mediates critical roles during neuronal lamination using the mouse retina as a model system. Down-regulation of mTORC1-signaling in retinal progenitor cells by conditional deletion of Rptor led to decreases in proliferation and increased apoptosis during embryogenesis. These developmental deficits preceded aberrant lamination in adult animals which was best exemplified by the fusion of the outer and inner nuclear layer and the absence of an outer plexiform layer. Moreover, ganglion cell axons originating from each Rptor-ablated retina appeared to segregate to an equal degree at the optic chiasm with both contralateral and ipsilateral projections displaying overlapping termination topographies within several retinorecipient nuclei. In combination, these visual pathway defects led to visually mediated behavioral deficits.Conclusions: This study establishes a critical role for mTORC1-signaling during retinal lamination and demonstrates that this pathway regulates diverse developmental mechanisms involved in driving the stratified arrangement of neurons during CNS development.
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42.
  • Nord, Hanna, et al. (författare)
  • Genetic compensation between Pax3 and Pax7 in zebrafish appendicular muscle formation
  • 2022
  • Ingår i: Developmental Dynamics. - : John Wiley & Sons. - 1058-8388 .- 1097-0177. ; 251:9, s. 1423-1438
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Migrating muscle progenitors delaminate from the somite and subsequently form muscle tissue in distant anatomical regions such as the paired appendages, or limbs. In amniotes, this process requires a signaling cascade including the transcription factor paired box 3 (Pax3).Results: In this study, we found that, unlike in mammals, pax3a/3b double mutant zebrafish develop near to normal appendicular muscle. By analyzing numerous mutant combinations of pax3a, pax3b and pax7a, and pax7b, we determined that there is a feedback system and a compensatory mechanism between Pax3 and Pax7 in this developmental process, even though Pax7 alone is not required for appendicular myogenesis. pax3a/3b/7a/7b quadruple mutant developed muscle-less pectoral fins.Conclusions: We found that Pax3 and Pax7 are redundantly required during appendicular myogenesis in zebrafish, where Pax7 is able to activate the same developmental programs as Pax3 in the premigratory progenitor cells.
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43.
  • Nunez-Leon, Daniel, et al. (författare)
  • Morphological diversity of integumentary traits in fowl domestication: Insights from disparity analysis and embryonic development
  • 2019
  • Ingår i: Developmental Dynamics. - : WILEY. - 1058-8388 .- 1097-0177. ; 248:11, s. 1044-1058
  • Forskningsöversikt (refereegranskat)abstract
    • The domestication of the fowl resulted in a large diversity of integumental structures in chicken breeds. Several integumental traits have been investigated from a developmental genetics perspective. However, their distribution among breeds and their developmental morphology remain unexplored. We constructed a discrete trait-breed matrix and conducted a disparity analysis to investigate the variation of these structures in chicken breeds; 20 integumental traits of 72 chicken breeds and the red junglefowl were assessed. The analyses resulted in slight groupings of breed types comparable to standard breed classification based on artificial selection and chicken type use. The red junglefowl groups together with bantams and European breeds. We provide new data on the red junglefowl and four chicken breeds, demonstrating where and when variation arises during embryonic development. We document variation in developmental timing of the egg tooth and feather formation, as well as other kinds of developmental patterning as in the anlagen of different type of combs. Changes in epithelial-mesenchymal signaling interactions may drive the highly diverse integument in chickens. Experimental and comparative work has revealed that the cranial neural crest mesenchyme mediates its interactions with the overlying epithelium and is the likely source of patterning that generates diversity in integumental structures.
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44.
  • O'Farrell, Fergal, et al. (författare)
  • Regulation of the Drosophila lin-41 Homologue dappled by let-7 Reveals Conservation of a Regulatory Mechanism Within the LIN-41 Subclade
  • 2008
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 237:1, s. 196-208
  • Tidskriftsartikel (refereegranskat)abstract
    • Drosophila Dappled (DPLD) is a member of the RBCC/TRIM superfamily, a protein family involved in numerous diverse processes such as developmental timing and asymmetric cell divisions. DPLD belongs to the LIN-41 subclade, several members of which are micro RNA (miRNA) regulated. We re-examined the LIN-41 subclade members and their relation to other RBCC/TRIMs and dpld paralogs, and identified a new Drosophila muscle specific RBCC/TRIM: Another B-Box Affiliate, ABBA. In silico predictions of candidate miRNA regulators of dpld identified let-7 as the strongest candidate. Overexpression of dpld led to abnormal eye development, indicating that strict regulation of dpld mRNA levels is crucial for normal eye development. This phenotype was sensitive to let-7 dosage, suggesting let-7 regulation of dpld in the eye disc. A cell-based assay verified let-7 miRNA down-regulation of dpld expression by means of its 3′-untranslated region. Thus, dpld seems also to be miRNA regulated, suggesting that miRNAs represent an ancient mechanism of LIN-41 regulation.
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45.
  • Ormestad, Mattias, 1974, et al. (författare)
  • Differences in the embryonic expression patterns of mouse Foxf1 and -2 match their distinct mutant phenotypes
  • 2004
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 229:2, s. 328-333
  • Tidskriftsartikel (refereegranskat)abstract
    • Murine genes encoding the forkhead transcription factors Foxf1 and -2 are both expressed in derivatives of the splanchnic mesoderm, i.e., the mesenchyme of organs derived from the primitive gut. In addition, Foxf2 is also expressed in limbs and the central nervous system. Targeted mutagenesis of Foxf1 and -2 suggests that Foxf1 is the more important of the two mammalian FoxF genes with early embryonic lethality of null embryos and a haploinsufficiency phenotype affecting foregut-derived organs. In contrast, the only reported defect in Foxf2 null embryos is cleft palate. To investigate if the differences in mutant phenotype can be attributed to nonoverlapping expression patterns or if distinct functions of the encoded proteins have to be inferred, we analyzed the early embryonic expression of Foxf2 and compared it with that of the better investigated Foxf1. We find that in the early embryo, Foxf1 is completely dominating-in terms of expression-in extraembryonic and lateral plate mesoderm, consistent with the malformations and early lethality of Foxf1 null mutants. Along the developing gut, Foxf1 is highly expressed throughout, whereas Foxf2 expression is concentrated to the posterior part-fitting the foregut haploinsufficiency phenotypes of Foxf1 mutants. Foxf2, on the other hand, is more prominent than Foxf1 in mesenchyme around the oral cavity, as would be predicted from the cleft palate phenotype. The differences in expression pattern also highlight areas where defects should be sought for in the Foxf2 mutant, for example limbs, the posterior gut, genitalia, and derivatives of the neural crest mesenchyme.
  •  
46.
  • Pandit, Tanushree, 1984-, et al. (författare)
  • BMP-induced L-Maf regulates subsequent BMP-independent differentiation of primary lens fibre cells
  • 2011
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 240:8, s. 1917-1928
  • Tidskriftsartikel (refereegranskat)abstract
    • Bone morphogenetic protein (BMP) signals are essential for lens development. However, the temporal requirement of BMP activity during early events of lens development has remained elusive. To investigate this question, we have used gain- and loss-of-function analyses in chick explant and intact embryo assays. Here, we show that BMP activity is both required and sufficient to induce L-Maf expression, whereas the onset of δ-crystallin and initial elongation of primary lens fibre cells are BMP-independent. Moreover, before lens placode formation and L-Maf onset, but not after, prospective lens placodal cells can switch to an olfactory placodal fate in response to decreased BMP activity. In addition, L-Maf is sufficient to up-regulate δ-crystallin independent of BMP signals. Taken together, these results show that before L-Maf induction BMP activity is required for lens specification, whereas after L-Maf up-regulation, the early differentiation of primary lens fibre cells occurs independent of BMP signals.
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47.
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48.
  • Rondon-Galeano, Maria, et al. (författare)
  • MAFBmodulates the maturation of lymphatic vascular networks in mice
  • 2020
  • Ingår i: Developmental Dynamics. - : WILEY. - 1058-8388 .- 1097-0177. ; 249:10, s. 1201-1216
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Lymphatic vessels play key roles in tissue fluid homeostasis, immune cell trafficking and in diverse disease settings. Lymphangiogenesis requires lymphatic endothelial cell (LEC) differentiation, proliferation, migration, and co-ordinated network formation, yet the transcriptional regulators underpinning these processes remain to be fully understood. The transcription factor MAFB was recently identified as essential for lymphangiogenesis in zebrafish and in cultured human LECs. MAFB is activated in response to VEGFC-VEGFR3 signaling and acts as a downstream effector. However, it remains unclear if the role of MAFB in lymphatic development is conserved in the mammalian embryo. Results We generated aMafbloss-of-function mouse using CRISPR/Cas9 gene editing.Mafbmutant mice presented with perinatal lethality associated with cyanosis. We identify a role for MAFB in modifying lymphatic network morphogenesis in the developing dermis, as well as developing and postnatal diaphragm. Furthermore, mutant vessels displayed excessive smooth muscle cell coverage, suggestive of a defect in the maturation of lymphatic networks. Conclusions This work confirms a conserved role for MAFB in murine lymphatics that is subtle and modulatory and may suggest redundancy in MAF family transcription factors during lymphangiogenesis.
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49.
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50.
  • Rosenberg, Louise C., et al. (författare)
  • The Transcriptional Activity of Neurog3 Affects Migration and Differentiation of Ectopic Endocrine Cells in Chicken Endoderm
  • 2010
  • Ingår i: Developmental Dynamics. - : Wiley. - 1097-0177 .- 1058-8388. ; 239:7, s. 1950-1966
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurog3 is expressed transiently in pancreatic endocrine progenitors where it is responsible for activating a transcription factor cascade which eventually defines the mature endocrine cells. However, the mechanism by which Neurog3 regulates different aspects of the endocrine differentiation program is less clear. In this report we used in ovo electroporation to investigate how manipulation of Neurog3 protein activity affected migration, differentiation and fate determination. We found that changes in the onset of Neurog3 expression only had minor effect on differentiation. However increasing the transcriptional activity of Neurog3 by fusing it to VP16 or co-electroporating with Ep300 caused the electroporated cells to migrate rather than differentiate. In contrast, reducing the transcriptional activity of Neurog3 by deleting parts of the activation domain, by fusing Neurog3 to the engrailed repressor domain, or co-electroporating with Hdac1 greatly increased the proportion of glucagon expressing cells. Developmental Dynamics 239:1950-1966, 2010. (C) 2010 Wiley-Liss, Inc.
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