Search

Tumor angiogenesis isrequired for tumor development and growth, and is regulatedby several factors including ROS. [H.sub.2][O.sub.2] is a ROS with an important role in cell signaling, but how [H.sub.2][O.sub.2] regulates tumor angiogenesis isstill poorly understood. We have xenografted tumor cells with altered levels of [H.sub.2][O.sub.2] by catalase overexpression into zebrafish embryos to study redox-induced tumor neovascularization. We found that vascular recruitment and invasion were impaired if catalase was overex-pressed. In addition, the overexpression of catalase altered the transcriptional levels of several angiogenesis-related factors in tumor cells, including TIMP-3 and THBS1. These two anti-angiogenic factors were found to be [H.sub.2][O.sub.2]-regulated by two different mechanisms: TIMP-3 expression in a cell-autonomous manner; and, THBS1 expression that was non-cell-autonomous. Our work shows that intracellular [H.sub.2][O.sub.2] regulates the expression of angiogenic factors and the formation of a vessel network. Understanding the molecular mechanisms that govern this multifunctional effectof[H.sub.2][O.sub.2] on tumor angiogenesis could beimportant for the development of more efficient anti-angiogenic therapies. Key words: hydrogen peroxide, zebrafish, tumor angiogenesis, catalase, TIMP-3, THBS1. Resume : L'angiogenese tumorale est necessaire au developpement et a la croissance des tumeurs et elle est regulee par plusieurs facteurs dont les derives reactifs d'oxygene (DRO). Le peroxyde d'hydrogene ([H.sub.2][O.sub.2]) est un DRO qui joue un role important dans la signalisation cellulaire, mais on comprend encore mal comment le [H.sub.2][O.sub.2] regule l'angiogenese tumorale. Les auteurs ont effectue des xenogreffes de cellules tumorales dont les niveaux de [H.sub.2][O.sub.2] sont modifies par la surexpression de la catalase dans des embryons de poisson-zebre afin d'etudier la neovascularisation tumorale induite par la redox. Ils ont trouve que le recrutement et l'invasion par les vaisseaux etaient attenues par la surexpression de la catalase. De plus, la surexpression de la catalase modifiait les niveaux de transcription de plusieurs facteurs relies a l'angiogenese dans les cellules tumorales dont TIMP-3 et THBS1. Il est apparu que ces deux facteurs anti-angiogeniques etaient regules par le [H.sub.2][O.sub.2] au moyen de deux mecanismes differents : l'expression de TIMP-3 est autonome a la cellule alors que l'expression de THBS1 est non-autonome. Le travail des auteurs montre que le [H.sub.2][O.sub.2] intracellulaire regule l'expression de facteurs angiogeniques et la formation d'un reseau vasculaire. La comprehension des mecanismes moleculaires qui gouvernent cet effet multifonctionnel du [H.sub.2][O.sub.2] sur l'angiogenese tumorale pourrait etre importante au developpement de nouvelles therapies anti-angiogeniques plus efficaces. [Traduit par la Redaction] Mots-cles : peroxyde d'hydrogene, poisson-zebre, angiogenese tumorale, catalase, TIMP-3, THBS1., Introduction Tumors originate from cellular masses with unchecked growth. As cells multiply, both the oxygen and nutrient supplies needed for cell survival and proliferation become limiting, leading to equilibrium between [...]

In the present investigation, nuclei of endodermal cells, primary and secondary mesenchyme cells (PMCs and SMCs), and small micromere descendants (SMDs) of the sea urchin Lytechinus variegatus were counted and mapped at five developmental stages, ranging from primary invagination to pluteus larva. The archenteron and its derivatives were measured three dimensionally with STERECON analytical software. For the first time SMC production is included in the kinetic analysis of archenteron formation. While the archenteron lumen doubled in length during secondary invagination, the number of archenteron cells increased by at least 38% (over 50% when SMCs that emigrated from the tip of the archenteron were included). The volume of the archenteron epithelial wall plus the volume of 17 new SMCs increased by 40% over the equivalent volumes at the end of primary invagination. Because secondary invagination involves the addition of archenteron cells and an increase in volume of the archenteron epithelium, we conclude that secondary invagination is not accomplished simply by the rearrangement and reshaping of the primary archenteron cells. Both archenteron cell number and wall volume continued to increase at the same rates from the end of secondary invagination until the 27-h prism stage, although the lumen lengthened more slowly. SMCs were also produced at a constant rate from primary invagination until the prism stage. Because the production of both endodermal and mesodermal cells continues until the late prism stage, we conclude that gastrulation (defined as the establishment of the germ layers) also extends into the late prism stage. Key Words: sea urchin; gastrulation; archenteron; 3D analysis; confocal microscopy.

Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish ( Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir. We evaluated drug metabolic profile by mass spectrometry, renal function with the inulin clearance assay, the 3D morphology of the proximal convoluted tubule by two-photon microscopy and the ultrastructure of proximal convoluted tubule mitochondria by transmission electron microscopy. Paracetamol was metabolized by conjugation and oxidation with further detoxification with glutathione. Renal clearance was reduced with gentamicin and paracetamol. Proximal tubules were enlarged with paracetamol and tenofovir. All drugs induced mitochondrial alterations including dysmorphic shapes ('donuts', 'pancakes' and 'rods'), mitochondrial swelling, cristae disruption and/or loss of matrix granules. These results are in agreement with the tubular effects of gentamicin, paracetamol and tenofovir in man and demonstrate that zebrafish larvae might be a good model to assess functional and structural damage associated with DIRI. [ABSTRACT FROM AUTHOR]

The Japanese quail is a widely used model organism for the study of embryonic development; however, anatomical resources are lacking. The Quail Anatomy Portal (QAP) provides 22 detailed three-dimensional (3D) models of quail embryos during development from embryonic day (E)1 to E15 generated using optical projection tomography. The 3D models provided can be virtually sectioned to investigate anatomy. Furthermore, using the 3D nature of the models, we have generated a tool to assist in the staging of quail samples. Volume renderings of each stage are provided and can be rotated to allow visualization from multiple angles allowing easy comparison of features both between stages in the database and between images or samples in the laboratory. The use of JavaScript, PHP and HTML ensure the database is accessible to users across different operating systems, including mobile devices, facilitating its use in the laboratory.The QAP provides a unique resource for researchers using the quail model. The ability to virtually section anatomical models throughout development provides the opportunity for researchers to virtually dissect the quail and also provides a valuable tool for the education of students and researchers new to the field. [ABSTRACT FROM AUTHOR]

Background: Skeletal myogenesis is extensively influenced by the surrounding environment. However, how the extracellular matrix (ECM) affects morphogenesis of muscles is not well understood. Results: We mapped the three-dimensional (3D) organization of fibronectin, tenascin, and laminin by immunofluorescence during early epaxial myogenesis in mouse embryos. We define four stages of dermomyotome/myotome development and reveal the 3D organization of myogenic cells within their ECM during those stages. Fibronectin is abundant in all interstitial tissues, while tenascin is restricted to intersegmental borders. Bundles of fibronectin and tenascin also penetrate into the myotome, possibly promoting myocyte alignment. A laminin matrix delineates the dermomyotome and myotome and undergoes dynamic changes, correlating with key developmental events. Conclusion: Our observations cast new light on how myotomal cells interact with their environment and suggest that, as the segmented myotomes transform into the epaxial muscle masses, the laminin matrix disassembles and myocytes use the abundant fibronectin matrix to reach their final organization. Developmental Dynamics 241:350-364, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]