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  • 1
    In: Development, The Company of Biologists, Vol. 113, No. 4 ( 1991-12-01), p. 1293-1304
    Abstract: This study investigates the primary effect of the eye lens obsolescence (Elo) gene of the mouse. Morphological features of the Elo lens were defined as follows: (1) deficient elongation of lens fiber cells, (2) morphological abnormality of nuclei of lens fiber cells, (3) lack of eosinophilic granules in the central fiber cells and (4) rupture of lens capsule in the posterior region. We have immunohistologically examined, by means of an in vivo BrdU incorporation system, whether or not the Elo gene regulates cell proliferation during lens development. The lens fiber cells were morphologically abnormal in day 13 embryonic Elo lens. However, there were no significant differences in morphology or cell proliferation between normal and Elo lens epithelium until day 14 of gestation. After day 15, the total cell number in the Elo lens epithelium was significantly less than that in the normal, but the total numbers of S-phase cells in the two genotypes were not significantly different. The ratio of the total S-phase cell number to the total number of lens epithelial cells may be affected by the developmental stage, but not directly by the genotype. The genotype, however, may be having a direct influence at later ages because malformation of Elo lens fiber cells must cause reduction of the total number of lens epithelial cells in older embryos. Although, at 30 days old, Elo lens cells were externally extruded through the ruptured capsule into the vitreous cavity, BrdU-labelled lens epithelial cells were detectable. To investigate whether the Elo lens phenotype is determined by its own genotype or by its cellular environment, we produced aggregation chimeras between C3H-Elo/+(C/C) and BALB/c (c/c). Most lenses of BALB/c dominant chimeras were oval in shape without the ruptured lens capsule. However, they were opaque in the center and slightly smaller in size than normal. The lenses of C3H-E/o/ + dominant chimeras were morphologically similar to the Elo lens. Although normal nuclei were regularly arranged in the anterior region, Elo-type nuclei were located in the posterior region. Immunohistological staining by using anti-C3H strain-specific antibody demonstrated that the lens fiber cells with abnormal nuclei were derived only from C3H-Elo/+, not from BALB/c. These observations suggest that the primary effect of the Elo gene in the developing lens may be specific to the fiber cell differentiation rather than to the cell proliferation. Moreover, the Elo gene may be autonomously expressed in the differentiating lens fiber cells, and intracellularly inhibit fiber cell elongation.
    Type of Medium: Online Resource
    ISSN: 0950-1991 , 1477-9129
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 1991
    detail.hit.zdb_id: 2007916-3
    SSG: 12
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  • 2
    In: Development, The Company of Biologists
    Abstract: Striated muscle cells in the tail of ascidian tadpole larvae differentiate cell-autonomously. Although several key regulatory factors have been identified, the genetic regulatory pathway has not fully been understood; comprehensive understanding of the regulatory pathway is essential for accurate modeling to deduce principles for gene regulatory network dynamics, and for comparative analysis how ascidians have evolved the cell-autonomous gene regulatory mechanism. Here, we revealed regulatory interactions among three key regulatory factors, Zic-r.b, Tbx6-r.b, and Mrf, and elucidated the mechanism by which these factors activate muscle structural genes. We revealed a cross-regulatory circuit among these regulatory factors, which maintained the expression of Tbx6-r.b and Mrf during gastrulation. While these two factors combinatorially activated muscle structural genes in late stage embryos, muscle structural genes were activated mainly by Tbx6-r.b before gastrulation. Time points when expression of muscle structural genes became first detectable were strongly correlated with the degree of Tbx6-r.b occupancy. Thus, the genetic pathway starting with Tbx6-r.b and Zic-r.b, which are activated by maternal factors and ending with expression of muscle structural genes, has been revealed.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2019
    detail.hit.zdb_id: 2007916-3
    SSG: 12
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  • 3
    In: Journal of Experimental Biology, The Company of Biologists
    Abstract: Several vertebrates, including fish, exhibit behavioural laterality and associated morphological asymmetry. Laterality may increase individual fitness, and foraging strength, accuracy, and speed. However, little is known about which behaviours are affected by laterality or what fish species exhibit obvious laterality. Previous research on the predatory behaviour of the scale-eating Lake Tanganyika cichlid Perissodus microlepis indicates behavioural laterality that reflects asymmetric jaw morphology. The Lake Malawi cichlid Genyochromis mento feeds on the fins of other fish, a behaviour that G. mento developed independently from the Tanganyikan Perissodini scale-eaters. We investigated stomach contents and behavioural laterality of predation in aquarium to clarify the functional roles and evolution of laterality in cichlids. We also compared the behavioural laterality and mouth asymmetry of G. mento and P. microlepis. The diet of G. mento mostly includes fin fragments, but also scales of several fish species. Most individual G. mento specimens showed significant attack bias favouring the skew mouth direction. However, there was no difference in success rate between attacks from the preferred side and those from the non-preferred side, and no lateralized kinetic elements in predation behaviour. G. mento showed weaker laterality than P. microlepis, partly because of their different feeding habits, the phylogenetic constraints from their shorter evolutionary history, and their origin from ancestor Haplochromini omnivorous/herbivorous species. Taken together, this study provides new insights into the functional roles of behavioural laterality: Predatory fish aiming for prey that show escape behaviours frequently exhibit lateralized behaviour in predation.
    Type of Medium: Online Resource
    ISSN: 1477-9145 , 0022-0949
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2018
    detail.hit.zdb_id: 1482461-9
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    The Company of Biologists ; 2010
    In:  Development Vol. 137, No. 10 ( 2010-05-15), p. 1755-1764
    In: Development, The Company of Biologists, Vol. 137, No. 10 ( 2010-05-15), p. 1755-1764
    Abstract: The Wingless (Wg)/Wnt signaling pathway is highly conserved throughout many multicellular organisms. It directs the development of diverse tissues and organs by regulating important processes such as proliferation, polarity and the specification of cell fates. Upon activation of the Wg/Wnt signaling pathway, Armadillo (Arm)/β-catenin is stabilized and interacts with the TCF family of transcription factors, which in turn activate Wnt target genes. We show here that Arm interacts with a novel BED (BEAF and Dref) finger protein that we have termed Sunspot (Ssp). Ssp transactivates Drosophila E2F-1 (dE2F-1) and PCNA expression, and positively regulates the proliferation of imaginal disc cells and the endoreplication of salivary gland cells. Wg negatively regulates the function of Ssp by changing its subcellular localization in the salivary gland. In addition, Ssp was found not to be involved in the signaling pathway mediated by Arm associated with dTCF. Our findings indicate that Arm controls development in part by regulating the function of Ssp.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2010
    detail.hit.zdb_id: 2007916-3
    SSG: 12
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  • 5
    In: Disease Models & Mechanisms, The Company of Biologists, Vol. 14, No. 3 ( 2021-03-01)
    Abstract: The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD. This article has an associated First Person interview with the first author of the paper.
    Type of Medium: Online Resource
    ISSN: 1754-8403 , 1754-8411
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2021
    detail.hit.zdb_id: 2451104-3
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  • 6
    In: Disease Models & Mechanisms, The Company of Biologists
    Abstract: Hypertrophic cardiomyopathy (HCM) is a hereditary disease characterized by cardiac hypertrophy with diastolic dysfunction. Gene mutations causing HCM have been found in about half of the patients, while the genetic etiology and pathogenesis remain unknown for many cases of HCM. To identify novel mechanisms underlying HCM pathogenesis, we generated a cardiovascular-mutant medaka fish non-spring heart (nsh), which showed diastolic dysfunction and hypertrophic myocardium. The nsh homozygotes had fewer myofibrils, disrupted sarcomeres and expressed pathologically stiffer titin isoforms. In addition, the nsh heterozygotes showed M-line disassembly that is similar to the pathological changes found in HCM. Positional cloning revealed a missense mutation in an immunoglobulin (Ig) domain located in the M-line-A-band transition zone of titin. Screening of mutations in 96 unrelated patients with familial HCM, who had no previously implicated mutations in known sarcomeric gene candidates, identified two mutations in Ig domains close to the M-line region of titin. In vitro studies revealed that the mutations found in both medaka fish and in familial HCM increased binding of titin to muscle-specific ring finger protein 1 (MURF1) and enhanced titin degradation by ubiquitination. These findings implicate an impaired interaction between titin and MURF1 as a novel mechanism underlying the pathogenesis of HCM.
    Type of Medium: Online Resource
    ISSN: 1754-8411 , 1754-8403
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2019
    detail.hit.zdb_id: 2451104-3
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  • 7
    In: Disease Models & Mechanisms, The Company of Biologists, Vol. 15, No. 7 ( 2022-07-01)
    Abstract: Serotonin (5-HT) is one of the key bioamines of nonalcoholic fatty liver disease (NAFLD). Its mechanism of action in autonomic neural signal pathways remains unexplained; hence, we evaluated the involvement of 5-HT and related signaling pathways via autonomic nerves in NAFLD. Diet-induced NAFLD animal models were developed using wild-type and melanocortin 4 receptor (MC4R) knockout (MC4RKO) mice, and the effects of the autonomic neural axis on NAFLD physiology, 5-HT and its receptors (HTRs), and lipid metabolism-related genes were assessed by applying hepatic nerve blockade. Hepatic neural blockade retarded the progression of NAFLD by reducing 5-HT in the small intestine, hepatic HTR2A and hepatic lipogenic gene expression, and treatment with an HTR2A antagonist reproduced these effects. The effects were milder in MC4RKO mice, and brain 5-HT and HTR2C expression did not correlate with peripheral neural blockade. Our study demonstrates that the autonomic liver-gut neural axis is involved in the etiology of diet-induced NAFLD and that 5-HT and HTR2A are key factors, implying that the modulation of the axis and use of HTR2A antagonists are potentially novel therapeutic strategies for NAFLD treatment. This article has an associated First Person interview with the first author of the paper.
    Type of Medium: Online Resource
    ISSN: 1754-8403 , 1754-8411
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2022
    detail.hit.zdb_id: 2451104-3
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  • 8
    In: Journal of Cell Science, The Company of Biologists, Vol. 116, No. 10 ( 2003-05-15), p. 2029-2038
    Abstract: Membrane-bound transferrin-like protein (MTf), a glycosylphosphatidylinositol-anchored protein, is expressed at high levels in many tumors and in several fetal and adult tissues including cartilage and the intestine, as well as in the amyloid plaques of Alzheimer's disease, although its role remains unknown. MTf is one of the major concanavalin A-binding proteins of the cell surface. In this study, we examined the effects of anti-MTf antibodies and concanavalin A on cell shape and gene expression,using cultures of chondrocytes and MTf-overexpressing ATDC5 and C3H10T1/2 cells. In cultures expressing MTf at high levels, concanavalin A induced cell-shape changes from fibroblastic to spherical cells, whereas no cell-shape changes were observed with wild-type ATDC5 or C3H10T1/2 cells expressing MTf at very low levels. The cell-shape changes were associated with enhanced proteoglycan synthesis and expression of cartilage-characteristic genes,including aggrecan and type II collagen. Some anti-MTf antibodies mimicked this action of concanavalin A, whereas other antibodies blocked the lectin action. The findings suggest that the crosslinking of MTf changes the cell shape and induces chondrogenic differentiation. MTf represents the first identification of a plant lectin receptor involved in cell-shape changes and the differentiation of animal cells.
    Type of Medium: Online Resource
    ISSN: 1477-9137 , 0021-9533
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2003
    detail.hit.zdb_id: 219171-4
    detail.hit.zdb_id: 1483099-1
    SSG: 12
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