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      Signals Which Build a Tubule

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          The phenomenon of branching morphogenesis is a fundamental process critical for development of several tubular organs including lung, mammary gland, and kidney. In the case of kidney, the ureteric bud (UB) that extends out from a pre-existing epithelial tube, the Wolffian duct, gives rise to the branched collecting duct system while the surrounding metanephric mesenchyme undergoes mesenchymal-epithelial transition to form the proximal parts of the nephron. These events are mediated by several soluble factors that act in a cooperative fashion either as pro or anti tubulogenic factors. Among the growing list of such molecules are the members of the FGF, TGF-β, and Wnt families as well as GDNF, HGF, and EGF. Cells respond to these soluble factors by initiating signaling pathways that regulate cell proliferation, cell migration and cell morphogenesis. These signaling pathways are also regulated in parallel by cell-cell and cell-matrix interactions, leading to the complex events necessary for tubule formation. Recent in-vitro and in-vivo studies have begun to shed light on the overall regulation of this phenomenon while the specific subcellular mechanisms are only beginning to be understood. This review focuses on our understanding of the morphogenic responses that regulate in-vitro tubulogenesis and how they may help us to ultimately understand this process in vivo in the kidney.

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          Most cited references 27

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          Convergence of Wnt, beta-catenin, and cadherin pathways.

           W Nelson,  Ferric Fang (2004)
          The specification and proper arrangements of new cell types during tissue differentiation require the coordinated regulation of gene expression and precise interactions between neighboring cells. Of the many growth factors involved in these events, Wnts are particularly interesting regulators, because a key component of their signaling pathway, beta-catenin, also functions as a component of the cadherin complex, which controls cell-cell adhesion and influences cell migration. Here, we assemble evidence of possible interrelations between Wnt and other growth factor signaling, beta-catenin functions, and cadherin-mediated adhesion.
            • Record: found
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            Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor.

            We have previously shown that Madin-Darby canine kidney (MDCK) epithelial cells grown in collagen gels in the presence of fibroblasts or fibroblast-conditioned medium (CM) form branching tubules, instead of the spherical cysts that develop under control conditions. We now report that the fibroblast-derived molecule responsible for epithelial tubulogenesis is hepatocyte growth factor (HGF). First, addition of exogenous HGF to cultures of MDCK cells induces formation of epithelial tubules. Second, the tubulogenic activity of fibroblast CM is completely abrogated by antibodies to HGF. These results demonstrate that HGF, a polypeptide that was identified as a mitogen for cultured hepatocytes, has the properties of a paracrine mediator of epithelial morphogenesis, and suggest that it may play important roles in the formation of parenchymal organs during embryonic development.
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              HGF/SF-met signaling in the control of branching morphogenesis and invasion.

               J Woude,  Yu Zhang (2003)
              Hepatocyte growth factor/Scatter factor (HGF/SF) is a multifunctional growth factor which can induce diverse biological events. In vitro, these include scattering, invasion, proliferation and branching morphogenesis. In vivo, HGF/SF is responsible for many processes during embryonic development and a variety of activities in adults, and many of these normal activities have been implicated in its role in tumorgenesis and metastasis. The c-Met receptor tyrosine kinase is the only known receptor for HGF/SF and mediates all HGF/SF induced biological activities. Upon HGF/SF stimulation, the c-Met receptor is tyrosine-phosphorylated which is followed by the recruitment of a group of signaling molecules and/or adaptor proteins to its cytoplasmic domain and its multiple docking sites. This action leads to the activation of several different signaling cascades that form a complete network of intra and extracellular responses. Different combinations of signaling pathways and signaling molecules and/or differences in magnitude of responses contribute to these diverse series of HGF/SF-Met induced activities and most certainly are influenced by cell type as well as different cellular environments. In this review, we focus on HGF/SF-induced branching morphogenesis and invasion, and bring together recent new findings which provide insight into how HGF/SF, via c-Met induces this response. Copyright 2002 Wiley-Liss, Inc.

                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                May 2005
                03 March 2005
                : 100
                : 1
                : e40-e45
                aDepartment of Nephrology, University of Freiburg, Freiburg, Germany; bSection of Nephrology, Yale University School of Medicine, New Haven, Conn., USA
                84111 Nephron Exp Nephrol 2005;100:e40–e45
                © 2005 S. Karger AG, Basel

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                Page count
                Figures: 1, References: 40, Pages: 1
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/84111

                Cardiovascular Medicine, Nephrology

                Growth factor, Kidney, MAPK, Tubulogenesis, Signaling


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