Rhomboid 3 orchestrates Slit-independent repulsion of tracheal branches at the CNS midline

Gallio, Marco; Englund, Camilla; Kylsten, Per; Samakovlis, Christos

doi:10.1242/dev.01242

Cited by 19 publications

(12 citation statements)

References 75 publications

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“…Other signaling pathways, including TGFβ/BMP, Wnt, and Robo/Slit, are required for specification of branch identity and/or regulation of subsequent outgrowth of specific branches (Vincent et al, 1997; Chen et al, 1998; Chihara and Hayashi, 2000; Llimargas, 2000; Englund et al, 2002; Gallio et al, 2004; Lundstrom et al, 2004). For example, the TGFβ/BMP pathway, activated by localized expression of the Dpp ligand, is required for specification of branches that migrate dorsally and ventrally (Vincent et al, 1997; Chen et al, 1998).…”

Section: Branching Morphogenesis: the Acquisition Of Complex Tube Arcmentioning

confidence: 99%

Morphogenesis of epithelial tubes: Insights into tube formation, elongation, and elaboration

Andrew

Ewald

2010

Developmental Biology

310

304

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Epithelial tubes are a fundamental tissue across the metazoan phyla and provide an essential functional component of many of the major organs. Recent work in flies and mammals has begun to elucidate the cellular mechanisms driving the formation, elongation and branching morphogenesis of epithelial tubes during development. Both forward and reverse genetic techniques have begun to identify critical molecular regulators for these processes and have revealed the conserved role of key pathways in regulating the growth and elaboration of tubular networks. In this review, we discuss the developmental programs driving the formation of branched epithelial networks, with specific emphasis on the trachea and salivary gland of Drosophila melanogaster and the mammalian lung, mammary gland, kidney, and salivary gland. We both highlight similarities in the development of these organs and attempt to identify tissue and organism specific strategies. Finally, we briefly consider how our understanding of the regulation of proliferation, apico-basal polarity, and epithelial motility during branching morphogenesis can be applied to understand the pathologic dysregulation of these same processes during metastatic cancer progression.

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Section: Branching Morphogenesis: the Acquisition Of Complex Tube Arcmentioning

confidence: 99%

Morphogenesis of epithelial tubes: Insights into tube formation, elongation, and elaboration

Andrew

Ewald

2010

Developmental Biology

310

304

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“…Initially, isolated in a genetic screen of embryonic developmental defects, rhomboids are essential for proper EGF receptor (EGFR) signaling in Drosophila . In fact, rhomboid and EGFR signaling is necessary for the development of the fly eye, trachea, and embryonic somatic musculature and many other places in the fly [7], [8], [15]–[17].…”

Section: Introductionmentioning

confidence: 99%

Affecting Rhomboid-3 Function Causes a Dilated Heart in Adult Drosophila

Lee

Lin

et al. 2010

PLoS Genet

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Drosophila is a well recognized model of several human diseases, and recent investigations have demonstrated that Drosophila can be used as a model of human heart failure. Previously, we described that optical coherence tomography (OCT) can be used to rapidly examine the cardiac function in adult, awake flies. This technique provides images that are similar to echocardiography in humans, and therefore we postulated that this approach could be combined with the vast resources that are available in the fly community to identify new mutants that have abnormal heart function, a hallmark of certain cardiovascular diseases. Using OCT to examine the cardiac function in adult Drosophila from a set of molecularly-defined genomic deficiencies from the DrosDel and Exelixis collections, we identified an abnormally enlarged cardiac chamber in a series of deficiency mutants spanning the rhomboid 3 locus. Rhomboid 3 is a member of a highly conserved family of intramembrane serine proteases and processes Spitz, an epidermal growth factor (EGF)–like ligand. Using multiple approaches based on the examination of deficiency stocks, a series of mutants in the rhomboid-Spitz–EGF receptor pathway, and cardiac-specific transgenic rescue or dominant-negative repression of EGFR, we demonstrate that rhomboid 3 mediated activation of the EGF receptor pathway is necessary for proper adult cardiac function. The importance of EGF receptor signaling in the adult Drosophila heart underscores the concept that evolutionarily conserved signaling mechanisms are required to maintain normal myocardial function. Interestingly, prior work showing the inhibition of ErbB2, a member of the EGF receptor family, in transgenic knock-out mice or individuals that received herceptin chemotherapy is associated with the development of dilated cardiomyopathy. Our results, in conjunction with the demonstration that altered ErbB2 signaling underlies certain forms of mammalian cardiomyopathy, suggest that an evolutionarily conserved signaling mechanism may be necessary to maintain post-developmental cardiac function.

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“…Migration of specific tracheal branches along distinct trajectories has been shown to require integrin signaling, EGF signaling, and at least one of the signaling pathways known to function in axonal pathfinding and SG migration, the Slit/Robo signaling cascade (Boube et al,2000; Englund et al,2002; Gallio et al,2004; Kolesnikov and Beckendorf,2005). The requirement for integrin signaling has been most clearly demonstrated in the migration of the visceral branch (VB) of the trachea along the visceral mesoderm (VM).…”

Section: Drosophila Tracheamentioning

confidence: 99%

Drosophila as a model for epithelial tube formation

Maruyama

Andrew

2011

Developmental Dynamics

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Summary Epithelial tubular organs are essential for life in higher organisms and include the pancreas and other secretory organs that function as biological factories for the synthesis and delivery of secreted enzymes, hormones and nutrients essential for tissue homeostasis and viability. The lungs, which are necessary for gas exchange, vocalization and maintaining blood pH, are organized as highly branched tubular epithelia. Tubular organs include arteries, veins and lymphatics, high-speed passageways for delivery and uptake of nutrients, liquids, gases and immune cells. The kidneys and components of the reproductive system are also epithelial tubes. Both the heart and central nervous system of many vertebrates begin as epithelial tubes. Thus, it is not surprising that defects in tube formation and maintenance underlie many human diseases. Accordingly, a thorough understanding how tubes form and are maintained is essential to developing better diagnostics and therapeutics. Among the best-characterized tubular organs are the Drosophila salivary gland and trachea, organs whose relative simplicity have allowed for in depth analysis of gene function, yielding key mechanistic insight into tube initiation, remodeling and maintenance. Here, we review our current understanding of salivary gland and trachea formation – highlighting recent discoveries into how these organs attain their final form and function.

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Rhomboid 3 orchestrates Slit-independent repulsion of tracheal branches at the CNS midline

Cited by 19 publications

References 75 publications

Morphogenesis of epithelial tubes: Insights into tube formation, elongation, and elaboration

Morphogenesis of epithelial tubes: Insights into tube formation, elongation, and elaboration

Affecting Rhomboid-3 Function Causes a Dilated Heart in Adult Drosophila

Drosophila as a model for epithelial tube formation

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