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\"This photo-illustrated book for early readers tells the story of a herd of zebras as they keep watch for predators and defend themselves against a lion.\"-- Provided by publisher.

Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center ( https://danio-code.zfin.org ) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis -regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals. The DANIO-CODE consortium leverages a large-scale multiomic dataset to improve zebrafish genome annotation. They identify ~140,000 cis -regulatory elements throughout development and perform a comparison with the mouse regulatory landscape.

Using simple text and color photographs, this book briefly describes the lives and habitats of zebras.

Background Lymphangiogenesis, the formation of lymphatic vessels, is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in vascular and lymphatic development in the zebrafish. Results We show that Sorbs1 is required for secondary sprouting and emergence of several vascular structures specifically derived from the axial vein. Most notably, formation of the precursor parachordal lymphatic structures is affected in sorbs1 mutant embryos, severely impacting the establishment of the trunk lymphatic vessel network. Interestingly, we show that Sorbs1 interacts with the BMP pathway and could function outside of Vegfc signaling. Mechanistically, Sorbs1 controls FAK/Src signaling and subsequently impacts on the cytoskeleton processes regulated by Rac1 and RhoA GTPases. Inactivation of Sorbs1 altered cell-extracellular matrix (ECM) contacts rearrangement and cytoskeleton dynamics, leading to specific defects in endothelial cell migratory and adhesive properties. Conclusions Overall, using in vitro and in vivo assays, we identify Sorbs1 as an important regulator of venous and lymphatic angiogenesis independently of the Vegfc signaling axis. These results provide a better understanding of the complexity found within context-specific vascular and lymphatic development.

Here it is shown that epithelia extrude live but not dying cells at sites of high strain, elucidating a mechanism for maintaining homeostatic cell numbers. Crowd control in epithelia For an epithelial-cell layer to retain its structure and provide a protective barrier, it needs to maintain a balance between the number of cells dividing and the number dying. Buzz Baum and colleagues study this process in Drosophila tissues and demonstrate a direct link between physical forces in a tissue and the rates of cell loss. In regions of tissue that are overcrowded, some of the cells undergo a loss of cell-adhesive junctions and are squeezed out by neighbouring cells. This process of live-cell delamination buffers epithelial cells against variations in growth and contributes to normal tissue homeostasis. As a link between epithelial hyperplasia and cell invasion, it may have relevance to the early stages of cancer development. In a second paper, Jody Rosenblatt and colleagues study epithelial-cell monolayers and find that epithelia extrude live but not dying cells at sites of high strain. The extruded cells undergo cell death owing to loss of survival factors. Hence, extrusion could provide a tumour-suppressive mechanism that could be used to eliminate excess cells. In carcinomas with high levels of survival signalling pathways, extrusion may promote tumour-cell invasion. For an epithelium to provide a protective barrier, it must maintain homeostatic cell numbers by matching the number of dividing cells with the number of dying cells. Although compensatory cell division can be triggered by dying cells 1 , 2 , 3 , it is unknown how cell death might relieve overcrowding due to proliferation. When we trigger apoptosis in epithelia, dying cells are extruded to preserve a functional barrier 4 . Extrusion occurs by cells destined to die signalling to surrounding epithelial cells to contract an actomyosin ring that squeezes the dying cell out 4 , 5 , 6 . However, it is not clear what drives cell death during normal homeostasis. Here we show in human, canine and zebrafish cells that overcrowding due to proliferation and migration induces extrusion of live cells to control epithelial cell numbers. Extrusion of live cells occurs at sites where the highest crowding occurs in vivo and can be induced by experimentally overcrowding monolayers in vitro . Like apoptotic cell extrusion, live cell extrusion resulting from overcrowding also requires sphingosine 1-phosphate signalling and Rho-kinase-dependent myosin contraction, but is distinguished by signalling through stretch-activated channels. Moreover, disruption of a stretch-activated channel, Piezo1, in zebrafish prevents extrusion and leads to the formation of epithelial cell masses. Our findings reveal that during homeostatic turnover, growth and division of epithelial cells on a confined substratum cause overcrowding that leads to their extrusion and consequent death owing to the loss of survival factors. These results suggest that live cell extrusion could be a tumour-suppressive mechanism that prevents the accumulation of excess epithelial cells.

Autophagy, an ancient and highly conserved intracellular degradation process, is viewed as a critical component of innate immunity because of its ability to deliver cytosolic bacteria to the lysosome. However, the role of bacterial autophagy in vivo remains poorly understood. The zebrafish (Danio rerio) has emerged as a vertebrate model for the study of infections because it is optically accessible at the larval stages when the innate immune system is already functional. Here, we have characterized the susceptibility of zebrafish larvae to Shigella flexneri, a paradigm for bacterial autophagy, and have used this model to study Shigella-phagocyte interactions in vivo. Depending on the dose, S. flexneri injected in zebrafish larvae were either cleared in a few days or resulted in a progressive and ultimately fatal infection. Using high resolution live imaging, we found that S. flexneri were rapidly engulfed by macrophages and neutrophils; moreover we discovered a scavenger role for neutrophils in eliminating infected dead macrophages and non-immune cell types that failed to control Shigella infection. We observed that intracellular S. flexneri could escape to the cytosol, induce septin caging and be targeted to autophagy in vivo. Depletion of p62 (sequestosome 1 or SQSTM1), an adaptor protein critical for bacterial autophagy in vitro, significantly increased bacterial burden and host susceptibility to infection. These results show the zebrafish larva as a new model for the study of S. flexneri interaction with phagocytes, and the manipulation of autophagy for anti-bacterial therapy in vivo.

\"This search-and-find book invites young readers to look for new vocabulary words and pictures while giving simple facts about a zebra's African habitat, body parts, and behaviors\"-- Provided by publisher.

A project to identify the phenotypes of disruptive mutations in every zebrafish protein-coding gene has so far revealed potentially disruptive mutations in more than 38% of the protein-coding genes, and the phenotypic consequences of each allele can be assessed using a novel multi-allelic phenotyping scheme. The zebrafish genome The genome of the zebrafish — a key model organism for the study of development and human disease — has now been sequenced and published as a well-annotated reference genome. Zebrafish turns out to have the largest gene set of any vertebrate so far sequenced, and few pseudogenes. Importantly for disease studies, comparison between human and zebrafish sequences reveals that 70% of human genes have at least one obvious zebrafish orthologue. A second paper reports on an ongoing effort to identify and phenotype disruptive mutations in every zebrafish protein-coding gene. Using the reference genome sequence along with high-throughput sequencing and efficient chemical mutagenesis, the project's initial results — covering 38% of all known protein-coding genes — they describe phenotypic consequences of more than 1,000 alleles. The long-term goal is the creation of a knockout allele in every protein-coding gene in the zebrafish genome. All mutant alleles and data are freely available at go.nature.com/en6mos . Since the publication of the human reference genome, the identities of specific genes associated with human diseases are being discovered at a rapid rate. A central problem is that the biological activity of these genes is often unclear. Detailed investigations in model vertebrate organisms, typically mice, have been essential for understanding the activities of many orthologues of these disease-associated genes. Although gene-targeting approaches 1 , 2 , 3 and phenotype analysis have led to a detailed understanding of nearly 6,000 protein-coding genes 3 , 4 , this number falls considerably short of the more than 22,000 mouse protein-coding genes 5 . Similarly, in zebrafish genetics, one-by-one gene studies using positional cloning 6 , insertional mutagenesis 7 , 8 , 9 , antisense morpholino oligonucleotides 10 , targeted re-sequencing 11 , 12 , 13 , and zinc finger and TAL endonucleases 14 , 15 , 16 , 17 have made substantial contributions to our understanding of the biological activity of vertebrate genes, but again the number of genes studied falls well short of the more than 26,000 zebrafish protein-coding genes 18 . Importantly, for both mice and zebrafish, none of these strategies are particularly suited to the rapid generation of knockouts in thousands of genes and the assessment of their biological activity. Here we describe an active project that aims to identify and phenotype the disruptive mutations in every zebrafish protein-coding gene, using a well-annotated zebrafish reference genome sequence 18 , 19 , high-throughput sequencing and efficient chemical mutagenesis. So far we have identified potentially disruptive mutations in more than 38% of all known zebrafish protein-coding genes. We have developed a multi-allelic phenotyping scheme to efficiently assess the effects of each allele during embryogenesis and have analysed the phenotypic consequences of over 1,000 alleles. All mutant alleles and data are available to the community and our phenotyping scheme is adaptable to phenotypic analysis beyond embryogenesis.