Inhibition of embryonic development by microcystin-LR in zebrafish, Danio rerio.

Microcystin-LR (MC-LR), a cyanobacterial toxin, is a potent inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A). PP1 and PP2A are critical regulators in embryonic development. However, the effects of MC-LR in embryonic development have been controversial. MC-LR has been demonstrated to be highly toxic in medaka, but not in zebrafish or rabbit embryos. The causes of difference may be due to membrane impermeability that impaired the delivery of MC-LR into cytoplasm of zebrafish and rabbit embryos. Therefore, we microinjected MC-LR directly into developing zebrafish embryos and investigated the effects of MC-LR on embryonic development. We demonstrated that MC-LR induced the lethality of zebrafish embryos in a dose- and time-dependent manner. MC-LR also induced the loss of blastomere coherence via the interference of beta-catenin and cadherins distributions. Furthermore, the MC-LR treated fry revealed various developmental defects. These results suggested that MC-LR might affect the phosphorylation equilibrium of signaling molecules, including beta-catenin and cadherins, required early in zebrafish embryonic development.     

Fish Dentitions as Paradigms for Odontogenic Questions

Bony fish, and in particular teleosts, represent a morphologically extremely diverse group of vertebrates, well suited to study certain problems in odontogenesis. In this article we address some questions that can benefit much from the use of fish dentitions as paradigms, such as endodermal participation in tooth formation and epithelial primacy in initiation events. Next, we highlight some results recently obtained in our laboratory with respect to two models, the zebrafish (Cyprinidae), and selected species of cichlids (Cichlidae). Finally, we pinpoint some questions that lend themselves admirably to be examined using fish models, such as the factors that control renewed initiation of teeth, and the relationship (or absence thereof) between Hox genes and tooth formation.     

Developmental defects in zebrafish for classification of EGF pathway inhibitors

One of the major challenges when testing drug candidates targeted at a specific pathway in whole animals is the discrimination between specific effects and unwanted, off-target effects. Here we used the zebrafish to define several developmental defects caused by impairment of Egf signaling, a major pathway of interest in tumor biology. We inactivated Egf signaling by genetically blocking Egf expression or using specific inhibitors of the Egf receptor function. We show that the combined occurrence of defects in cartilage formation, disturbance of blood flow in the trunk and a decrease of myelin basic protein expression represent good indicators for impairment of Egf signaling. Finally, we present a classification of known tyrosine kinase inhibitors according to their specificity for the Egf pathway.     

Animal models of fibrodysplasia ossificans progressiva

Fibrodysplasia Ossificans Progressiva is a rare human disease of heterotopic ossification. FOP patients experience progressive development of ectopic bone within fibrous tissues that contributes to a gradual loss of mobility and can lead to early mortality. Due to lack of understanding of the etiology and progression of human FOP, and the fact that surgical interventions often exacerbate FOP disease progression, alternative therapeutic methods are needed, including modeling in animals, to study and improve understanding of human FOP. In this review we provide an overview of the existing animal models of FOP and the key mechanistic findings from each. In addition, we highlight the specific advantages of a new adult zebrafish model, generated by our lab, to study human FOP. Developmental Dynamics 247:279–288, 2018. © 2017 Wiley Periodicals, Inc.     

Comparative studies of Toll-like receptor signalling using zebrafish

Zebrafish model systems for infectious disease are increasingly used for the functional analysis of molecular pattern recognition processes. These studies benefit from the high conservation level of all innate immune factors in vertebrates. Zebrafish studies are strategically well positioned for this because of the ease of comparisons with studies in other fish species of which the immune system also has been intensively studied, but that are currently still less amendable to detailed genetic or microscopic studies. In this paper we focus on Toll-like receptor (TLR) signalling factors, which currently are the best characterized in mammalian systems. We review the knowledge on TLR signalling in the context of recent advances in zebrafish studies and discuss possibilities for future approaches that can complement studies in cell cultures and rodent models. A focus in these comparisons is the role of negative control mechanisms in immune responses that appear very important in a whole organism to keep adverse systemic responses in check. We also pay much attention to comparisons with studies in common carp that is highly related to zebrafish and that because of its large body mass can complement immune studies in zebrafish.     

斑马鱼资源的开发保藏与国家斑马鱼资源中心

斑马鱼是一种新兴的脊椎模式动物.在过去的30年中,斑马鱼已被广泛应用于生命科学、健康科学、环境农业等诸多科研领域.为了满足不同的科研需要,研究人员开发和利用各种技术创建了大量的斑马鱼基因突变和转基因品系,这些品系已成为开展相关科学研究的宝贵资源.为了更好地保藏和利用这些资源,在全球范围内建设有多个规模不一的斑马鱼资源库.2012年,我国的国家斑马鱼资源中心(http://zfish.cn)在中国科学院水生生物研究所正式成立.本文将重点介绍全球斑马鱼资源的开发和保藏情况,以及我国国家斑马鱼资源中心的最新建设进展.     

Novel dose-dependent alterations in excitatory GABA during embryonic development associated with lead (Pb) neurotoxicity

Lead (Pb) is a heavy metal that is toxic to numerous physiological processes. Its use in industrial applications is widespread and results in an increased risk of human environmental exposure. The central nervous system (CNS) is most sensitive to Pb exposure during early development due to rapid cell proliferation and migration, axonal growth, and synaptogenesis. One of the key components of CNS development is the Gamma-aminobutyric acid (GABA)-ergic system. GABA is the primary inhibitory neurotransmitter in the adult brain. However, during development GABA acts as an excitatory neurotrophic factor which contributes to these cellular processes. Multiple studies report effects of Pb on GABA in the mature brain; however, little is known regarding the adverse effects of Pb exposure on the GABAergic system during embryonic development. To characterize the effects of Pb on the GABAergic system during development, zebrafish embryos were exposed to 10, 50, or 100 ppb Pb or a control treatment. Tissue up-take, gross morphological alterations, gene expression, and neurotransmitter levels were analyzed. Analysis revealed that alterations in gene expression throughout the GABAergic system and GABA levels were dose and developmental time point specific. These data provide a framework for further analysis of the effects of Pb on the GABAergic system during the excitatory phase and as GABA transitions to an inhibitory neurotransmitter during development.     

A statistical assembled deformable model (SAMTUS) for vasculature reconstruction

Although many deformable models have been proposed in medical applications for segmenting isolated structures in the human anatomy, not much of such work had been done on tubular structures such as the vasculature. In this paper, we propose a statistical assembled model for tubular structures (SAMTUS) to segment entire tubular structure from three-dimensional (3D) volumetric data. To our knowledge, there is no literature about the statistical deformable model for entire tubular structures. Specifically, the statistical tubular model is composed of a statistical axis model (SAM) and a statistical surface model (SSM). Both of them are assembled from a set of branch segments through the control points. Instead of searching for fuzzy correspondence along tubular axes or surfaces, we build point matching between feature points along tubular segments, and train SAM and SSM independently to characterize, respectively, the axial and the cross-sectional variation of the entire structure. In this way, more accurate point correspondence can be established, and a larger number of deformation modes can be captured. Our SAMTUS-based segmentation process consists of three stages: initialization, model fitting and final refinement. The experimental results demonstrate that the algorithm obtains good quantifications on the morphology and volume of the vasculature of the zebrafish which is being used increasingly as a specimen for drug screening and genomic research.     

Identification of environmental chemicals that induce yolk malabsorption in zebrafish using automated image segmentation

Environmental factors affecting nutrient availability during development can cause predisposition to diseases later in life. To identify chemicals in the environment capable of altering nutrient mobilization, we analyzed yolk malabsorption in the zebrafish embryo, which relies on maternally-derived yolk for nutrition during its first week of life. Embryos of the transgenic zebrafish line HGn50D, which fluoresce in the yolk syncytial layer, were exposed from two to five days post fertilization to different chemicals. We developed a software package to automatically and accurately segment and quantify the area of the fluorescing yolk in images captured at the end of the treatment period. Based on this quantification, we found that prochloraz decreased yolk absorption, while butralin, tetrabromobisphenol A, tetrachlorobisphenol A and tributyltin increased yolk absorption. Given the number and variety of industrial chemicals in commerce today, development of automated image processing to perform high-speed quantitative analysis of biological effects is an important step for enabling high throughput screening to identify chemicals altering nutrient absorption.