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Giovanni Vitale, Germano Gaudenzi, Alessandra Dicitore, Franco Cotelli, Diego Ferone, and Luca Persani

Introduction In the past decades zebrafish ( Danio rerio ) has emerged as a powerful vertebrate model system to study vertebrate developmental mechanisms. Indeed, zebrafish has a high fecundity (a female can lay up to 100–200 eggs/week), the embryos

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Margo Dona, Selma Waaijers, Susan Richter, Graeme Eisenhofer, Jeroen Korving, Sarah M Kamel, Jeroen Bakkers, Elena Rapizzi, Richard J Rodenburg, Jan Zethof, Marnix Gorissen, Gert Flik, Peter M T Deen, and Henri J L M Timmers

signaling, failed to mimic the human diseased phenotype. In contrast to Vhl knock-out mice, however, homozygous vhl mutant zebrafish did develop key aspects of the human disease condition, including polycythemia and severe neovascularization, a prominent

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Germano Gaudenzi, Silvia Carra, Alessandra Dicitore, Maria Celeste Cantone, Luca Persani, and Giovanni Vitale

progression. Although rodents represent the main animal model in cancer research, the use of this model in the field of NETs is very limited. In the last decade, the use of zebrafish ( Danio rerio ) in biomedical research is growing exponentially, with

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Caitlin Bourque and Yariv Houvras

Introduction: endocrine tissues in zebrafish Zebrafish have most organs found in higher vertebrates, including endocrine tissues. Development in zebrafish proceeds rapidly, the embryos are translucent and can be studied using light microscopy, and

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Tirtha K Das and Ross L Cagan

development, neurobiology and disease, Caenorhabditis elegans , Drosophila and zebrafish have provided important mechanistic and therapeutic information. The purpose of these models is not to replace mammalian models but to complement them. For example

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Giovanni Vitale, Germano Gaudenzi, Luisa Circelli, Marco F Manzoni, Andrea Bassi, Niccolò Fioritti, Antongiulio Faggiano, Annamaria Colao, and on behalf of NIKE Group

experiments are extended after 15 days of incubation ( Staton et al . 2009 , Ribatti 2016 ). Zebrafish Another powerful animal model that can help the preclinical research on MTC is zebrafish ( Danio rerio ). This small teleostean fish emerged as a

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Hermine Mohr and Natalia S Pellegata

the most frequent mutations, as highlighted in (A). Menin is highly conserved among species, with a 97, 97, 67 and 45% sequence homology between human and mouse, rat, zebrafish or fly, respectively ( Fig. 1B ). Two important Menin’s binding

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Jason Hatakeyama, Jessica H Wald, Ignat Printsev, Hsin-Yi Henry Ho, and Kermit L Carraway III

function. In vertebrates, most developmental studies have focused on Vangl2. Alterations to Vangl2 lead to severe developmental defects in multiple organs, providing fundamental insight into PCP function. Most notably, depletion of Vangl2 in zebrafish

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D S Saloman, C Bianco, A D Ebert, N I Khan, M De Santis, N Normanno, C Wechselberger, M Seno, K Williams, M Sanicola, S Foley, W J Gullick, and G Persico

The EGF-CFC gene family encodes a group of structurally related proteins that serve as important competence factors during early embryogenesis in Xenopus, zebrafish, mice and humans. This multigene family consists of Xenopus FRL-1, zebrafish one-eyed-pinhead (oep), mouse cripto (Cr-1) and cryptic, and human cripto (CR-1) and criptin. FRL-1, oep and mouse cripto are essential for the formation of mesoderm and endoderm and for correct establishment of the anterior/posterior axis. In addition, oep and cryptic are important for the establishment of left-right (L/R) asymmetry. In zebrafish, there is strong genetic evidence that oep functions as an obligatory co-factor for the correct signaling of a transforming growth factor-beta (TGFbeta)-related gene, nodal, during gastrulation and during L/R asymmetry development. Expression of Cr-1 and cryptic is extinguished in the embryo after day 8 of gestation except for the developing heart where Cr-1 expression is necessary for myocardial development. In the mouse, cryptic is not expressed in adult tissues whereas Cr-1 is expressed at a low level in several different tissues including the mammary gland. In the mammary gland, expression of Cr-1 in the ductal epithelial cells increases during pregnancy and lactation and immunoreactive and biologically active Cr-1 protein can be detected in human milk. Overexpression of Cr-1 in mouse mammary epithelial cells can facilitate their in vitro transformation and in vivo these Cr-1-transduced cells produce ductal hyperplasias in the mammary gland. Recombinant mouse or human cripto can enhance cell motility and branching morphogenesis in mammary epithelial cells and in some human tumor cells. These effects are accompanied by an epithelial-mesenchymal transition which is associated with a decrease in beta-catenin function and an increase in vimentin expression. Expression of cripto is increased several-fold in human colon, gastric, pancreatic and lung carcinomas and in a variety of different types of mouse and human breast carcinomas. More importantly, this increase can first be detected in premalignant lesions in some of these tissues. Although a specific receptor for the EGF-CFC proteins has not yet been identified, oep depends upon an activin-type RIIB and RIB receptor system that functions through Smad-2. Mouse and human cripto have been shown to activate a ras/raf/MAP kinase signaling pathway in mammary epithelial cells. Activation of phosphatidylinositol 3-kinase and Akt are also important for the ability of CR-1 to stimulate cell migration and to block lactogenic hormone-induced expression of beta-casein and whey acidic protein. In mammary epithelial cells, part of these responses may depend on the ability of CR-1 to transactivate erb B-4 and/or fibroblast growth factor receptor 1 through an src-like tyrosine kinase.

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Katharina Lampichler, Patricio Ferrer, Greisa Vila, Mirjam I Lutz, Florian Wolf, Engelbert Knosp, Ludwig Wagner, Anton Luger, and Sabina Baumgartner-Parzer

pituitary development because downregulation of the Hh pathway in mice results in pituitary hypoplasia ( Treier et al . 2001 ). Similar effects could be seen in zebrafish in which attenuation of the Hh signaling severely disrupts pituitary organogenesis