Genetic control of epithelial tube fusion during Drosophila tracheal development

Department of Biochemistry, Stanford University School of Medicine, CA 94305, USA.
Development (Impact Factor: 6.46). 12/1996; 122(11):3531-6.
Source: PubMed


During development of tubular networks such as the mammalian vascular system, the kidney and the Drosophila tracheal system, epithelial tubes must fuse to each other to form a continuous network. Little is known of the cellular mechanisms or molecular control of epithelial tube fusion. We describe the cellular dynamics of a tracheal fusion event in Drosophila and identify a gene regulatory hierarchy that controls this extraordinary process. A tracheal cell located at the developing fusion point expresses a sequence of specific markers as it grows out and contacts a similar cell from another tube; the two cells adhere and form an intercellular junction, and they become doughnut-shaped cells with the lumen passing through them. The early fusion marker Fusion-1 is identified as the escargot gene. It lies near the top of the regulatory hierarchy, activating the expression of later fusion markers and repressing genes that promote branching. Ectopic expression of escargot activates the fusion process and suppresses branching throughout the tracheal system, leading to ectopic tracheal connections that resemble certain arteriovenous malformations in humans. This establishes a simple genetic system to study fusion of epithelial tubes.

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Available from: Christos Samakovlis,
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    • "The tracheal system originates from epithelial placodes that invaginate and generate an interconnected network of branches through migration, cell shape changes and fusions. During larval development the terminal tracheal cells branch extensively, forming a highly ramified network of terminal branches with subcellular tubes [52]–[56]. A fibroblast growth factor signaling pathway, using the ligand Branchless (FGF) and the receptor Breathless (Btl), and operating through the canonical Ras/Raf/MEK/MAPK cascade, is used repeatedly during the different stages of tracheal development [54], [55], [57]–[59]. "
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    ABSTRACT: A key element in the regulation of subcellular branching and tube morphogenesis of the Drosophila tracheal system is the organization of the actin cytoskeleton by the ERM protein Moesin. Activation of Moesin within specific subdomains of cells, critical for its interaction with actin, is a tightly controlled process and involves regulatory inputs from membrane proteins, kinases and phosphatases. The kinases that activate Moesin in tracheal cells are not known. Here we show that the Sterile-20 like kinase Slik, enriched at the luminal membrane, is necessary for the activation of Moesin at the luminal membrane and regulates branching and subcellular tube morphogenesis of terminal cells. Our results reveal the FGF-receptor Breathless as an additional necessary cue for the activation of Moesin in terminal cells. Breathless-mediated activation of Moesin is independent of the canonical MAP kinase pathway.
    PLoS ONE 07/2014; 9(7):e103323. DOI:10.1371/journal.pone.0103323 · 3.23 Impact Factor
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    • "In this configuration, a new challenge appears for generating a continuous tube: connecting luminal compartments emerging between the consecutive cells, without altering the integrity of the structure and causing the lumen to enter into contact with other compartments. In Drosophila trachea, the problem is solved by a fusion/fission event between the two membrane domains of the cell that are in contact with the two separate lumen pockets, creating a central hole that allows the two lumen pockets to merge (Samakovlis et al., 1996). We recently developed a new model for in vivo studies of tubulogenesis, the notochord of Ciona intestinalis, which provides a simple system to explore this process. "
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    ABSTRACT: Apico-basal polarization is a crucial step in the de novo formation of biological tubes. In Ciona notochord, tubulogenesis occurs in a single file of cells in the absence of cell proliferation. This configuration presents a unique challenge for the formation of a continuous lumen. Here, we show that this geometric configuration is associated with a novel polarization strategy: the generation of bipolar epithelial cells possessing two apical/luminal domains instead of one, as in the conventional epithelium. At the molecular level, cells establish two discrete Par3/Par6/aPKC patches, and form two sets of tight junctions, in opposite points of the cells. The key molecule controlling the formation of both domains is Par3. Changing the position of the cells within the organ fundamentally changes their polarity and the number of apical domains they develop. These results reveal a new mechanism for tubulogenesis from the simplest cell arrangement, which occurs in other developmental contexts, including vertebrate vascular anastomosis.
    Development 06/2013; 140(14). DOI:10.1242/dev.092387 · 6.46 Impact Factor
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    • "As the dorsal branch extends, one of the cells of the branch comes in contact with a cell from the neighboring branch and binds to it, thus fusing the branches to form a contiguous airway [9]. Notch signaling again plays a similar role by aiding Bnl and Dpp and ordaining the fusion cell fate [16,18,19]. "
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    ABSTRACT: The assembly of cells into tissues is a complex process controlled by numerous signaling pathways to ensure the fidelity of the final structure. Tissue assembly is also very dynamic, as exemplified by the formation of branched organs. Here we present two examples of tissue assembly in branched systems that highlight this dynamic nature: formation of the tracheal network in Drosophila melanogaster and the ducts of the mammary gland in mice. Extension of the branches during tracheal development is a stereotyped process that produces identical organ geometries across individuals, whereas elongation of the ducts of the pubertal mammary gland is a non-stereotyped process that produces unique patterns. By studying these two organs, we can begin to understand the dynamic nature of development of other stereotyped and non-stereotyped branching systems, including the lung, kidney, and salivary gland.
    Stem Cell Research & Therapy 10/2012; 3(5):42. DOI:10.1186/scrt133 · 3.37 Impact Factor
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