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Showing papers by "Massimo Santoro published in 2014"


Journal ArticleDOI
03 Mar 2014-PLOS ONE
TL;DR: The data suggests that zebrafish mural cells develop relatively late, and have little mobility once they associate with vessels.
Abstract: Mural cells of the vascular system include vascular smooth muscle cells (SMCs) and pericytes whose role is to stabilize and/or provide contractility to blood vessels. One of the earliest markers of mural cell development in vertebrates is α smooth muscle actin (acta2; αsma), which is expressed by pericytes and SMCs. In vivo models of vascular mural cell development in zebrafish are currently lacking, therefore we developed two transgenic zebrafish lines driving expression of GFP or mCherry in acta2-expressing cells. These transgenic fish were used to trace the live development of mural cells in embryonic and larval transgenic zebrafish. acta2:EGFP transgenic animals show expression that largely mirrors native acta2 expression, with early pan-muscle expression starting at 24 hpf in the heart muscle, followed by skeletal and visceral muscle. At 3.5 dpf, expression in the bulbus arteriosus and ventral aorta marks the first expression in vascular smooth muscle. Over the next 10 days of development, the number of acta2:EGFP positive cells and the number of types of blood vessels associated with mural cells increases. Interestingly, the mural cells are not motile and remain in the same position once they express the acta2:EGFP transgene. Taken together, our data suggests that zebrafish mural cells develop relatively late, and have little mobility once they associate with vessels.

81 citations


Journal ArticleDOI
TL;DR: The most recent methods and studies on cell metabolism are summarized, which support the overall value for the zebrafish model system not only to study metabolism but also metabolic disease states.
Abstract: Cell metabolism plays a key role in many essential biological processes. The recent availability of novel technologies and organisms to model cell metabolism in vivo is expanding current knowledge of cell metabolism. In this context, the zebrafish (Danio rerio) is emerging as a valuable model system to learn about the metabolic routes critical for cellular homeostasis. Here, the most recent methods and studies on cell metabolism are summarized, which support the overall value for the zebrafish model system not only to study metabolism but also metabolic disease states. It is envisioned that this small vertebrate system will help in the understanding of pathogenesis for numerous metabolic-related disorders in humans and in the identification of their therapeutic treatments.

43 citations


Journal ArticleDOI
TL;DR: The zebrafish model is seen as an important system that can possibly complement well-established mouse models in cancer research to generate novel insights into the molecular mechanism of the tumor angiogenesis.
Abstract: The process of de novo vessel formation, called angiogenesis, is essential for tumor progression and spreading. Targeting of molecular pathways involved in such tumor angiogenetic processes by using specific drugs or inhibitors is important for developing new anticancer therapies. Drug discovery remains to be the main focus for biomedical research and represents the essence of antiangiogenesis cancer research. To pursue these molecular and pharmacological goals, researchers need to use animal models that facilitate the elucidation of tumor angiogenesis mechanisms and the testing of antiangiogenic therapies. The past few years have seen the zebrafish system emerge as a valid model organism to study developmental angiogenesis and, more recently, as an alternative vertebrate model for cancer research. In this review, we will discuss why the zebrafish model system has the advantage of being a vertebrate model equipped with easy and powerful transgenesis as well as imaging tools to investigate not only physiological angiogenesis but also tumor angiogenesis. We will also highlight the potential of zebrafish for identifying antitumor angiogenesis drugs to block tumor development and progression. We foresee the zebrafish model as an important system that can possibly complement well-established mouse models in cancer research to generate novel insights into the molecular mechanism of the tumor angiogenesis.

32 citations


Journal ArticleDOI
TL;DR: From an MCR fragment library, two novel chemical series have been developed as inhibitors of RET, which is a kinase involved in the pathology of medullary thyroid cancer (MTC), and 6g was confirmed to be a Type-II RET inhibitor.

19 citations