In Vivo Imaging Reveals Different Cellular Functions for FGF and Dpp Signaling in Tracheal Branching Morphogenesis

Ribeiro, Carlos; Ebner, Andreas; Affolter, Markus

doi:10.1016/s1534-5807(02)00171-5

Cited by 148 publications

(137 citation statements)

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“…Overexpression of the FGFR in all tracheal cells results in ectopic filopodia extension from the stalk, indicating that FGFR levels and activity underly the distinction between tip and stalk cell behavior and fate. 4,5 In attempts to understand the process of angiogenic sprouting, early imaging of salamander tails in the 1930s provided the first notion of dynamic protrusive behavior at the tip of each vascular sprout; subsequently, detailed images of vascular sprouts in the developing CNS identified elaborate filopodia extension from the sprout tip, leading the authors to speculate that specific tip cells, which extend these filopodia, function to read guidance cues in the tissue during the sprouting process (refs. 6-8, and references therein).…”

Section: Mechanics Of Angiogenic Sproutingmentioning

confidence: 99%

VEGF and endothelial guidance in angiogenic sprouting

2008

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The cellular actions of VEGF need to be coordinated to guide vascular patterning during sprouting angiogenesis. Individual endothelial tip cells lead and guide the blood vessel sprout, while neighbouring stalk cells proliferate and form the vascular lumen. Recent studies illustrate how endothelial DLL4/NOTCH signalling, stimulated by VEGF, regulates the sprouting response by limiting tip cell formation in the stalk. The spatial distribution of VEGF, in turn, regulates the shape of the ensuing sprout by directing tip cell migration and determining stalk cell proliferation.

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Section: Mechanics Of Angiogenic Sproutingmentioning

confidence: 99%

VEGF and endothelial guidance in angiogenic sprouting

2008

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“…Cells at the tip of tracheal branches (so-called tip cells) appear to be highly dynamic when visualized in live embryos with confocal microscopy; they send out filopodia and lamellipodia in response to Btl/Fgfr signalling. Stalk cells, which link the tip cells to the other tracheal branches, do not form such extensions (Ribeiro et al, 2002) (Fig. 3).…”

Section: The Role Of Cell Migrationmentioning

confidence: 99%

Section: The Role Of Cell Migrationmentioning

confidence: 99%

“…3). In the complete absence of Fgfr signalling, cells remain in the saclike configuration, and filopodia or lamellipodia are not seen (Ribeiro et al, 2002), demonstrating that Bnl/Fgf signalling regulates both the motility and the directionality of tracheal cell movement in the embryo.Another important role of Fgf signalling during the branching process is the induction of Notch signalling. High levels of Fgf signalling in the tip cell of primary branches lead to the activation of the Notch (N) ligand Delta (Dl) (Llimargas, 1999;Steneberg et al, 1999;Ikeya and Hayashi, 1999).…”

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Tracheal branching morphogenesis inDrosophila: new insights into cell behaviour and organ architecture

2008

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2055Our understanding of the molecular control of morphological processes has increased tremendously over recent years through the development and use of high resolution in vivo imaging approaches, which have enabled cell behaviour to be linked to molecular functions. Here we review how such approaches have furthered our understanding of tracheal branching morphogenesis in Drosophila, during which the control of cell invagination, migration, competition and rearrangement is accompanied by the sequential secretion and resorption of proteins into the apical luminal space, a vital step in the elaboration of the trachea's complex tubular network. We also discuss the similarities and differences between flies and vertebrates in branched organ formation that are becoming apparent from these studies. IntroductionBranching morphogenesis restructures epithelial sheets to give rise to organs of fascinating three-dimensional architecture, as exemplified by the adult lung, the kidney and the vasculature in humans. In Drosophila melanogaster, genetic studies have provided much insight into the regulatory networks that regulate the ordered formation of tracheal branches in the embryo, and into how the different branches coordinate their relative sizes, an issue that is of importance to the physical aspects of branched organ function (Affolter et al., 2003;Ghabrial et al., 2003;Uv et al., 2003). More recently, the development of live-imaging approaches in Drosophila have allowed researchers to take a deeper look at the behaviour of cells during the branching process, and have enabled events at the molecular level to be linked to the behaviour of individual cells or groups of cells.This combination of molecular genetics and live-imaging techniques has provided investigators with a unique opportunity to understand the morphological processes that occur during branching morphogenesis. This review focuses and builds on some of these recent insights, and assesses how they have led to a better understanding of the cellular and molecular processes that contribute to the transformation of simple, two-dimensional epithelial sheets into fascinating, three-dimensional tubular structures that can perform important functions in development and homeostasis. We focus here on the Drosophila tracheal system because several cellular and molecular paradigms, such as cell migration, competition and rearrangement, as well as the elaboration of a complex apical luminal environment, have recently been uncovered in this system that might serve related roles in the formation of other branched organs or tissues; these similarities might help us in the future to gain an even better understanding of how morphogenesis in general is regulated during development. Tracheal development in the fly embryoThe complex structure of the tracheal system consists of interconnected, metameric units of different-sized tubes that extend over the entire embryo shortly before hatching (Samakovlis et al., 1996b) (see Fig. 1, see also Movie 1 in the supplementary material)....

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“…Guanine nucleotide exchange factors (GEFs) act upstream of Rho GTPases and promote their local activation in the cell. Although FGFRs might be required and sufficient for the formation of filopodial protrusions, as shown for tracheal cell migration in Drosophila (Ribeiro et al, 2002), the molecules that connect FGFR signaling pathways to…”

Section: Introductionmentioning

confidence: 99%

The RhoGEF Pebble is required for cell shape changes during cell migration triggered by theDrosophilaFGF receptor Heartless

et al. 2004

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The FGF receptor Heartless (HTL) is required for mesodermal cell migration in the Drosophila gastrula. We show that mesoderm cells undergo different phases of specific cell shape changes during mesoderm migration. During the migratory phase, the cells adhere to the basal surface of the ectoderm and exhibit extensive protrusive activity. HTL is required for the protrusive activity of the mesoderm cells. Moreover, the early phenotype of htl mutants suggests that HTL is required for the adhesion of mesoderm cells to the ectoderm.In a genetic screen we identified pebble (pbl) as a novel gene required for mesoderm migration. pbl encodes a guanyl nucleotide exchange factor (GEF) for RHO1 and is known as an essential regulator of cytokinesis. We show that the function of PBL in cell migration is independent of the function of PBL in cytokinesis. Although RHO1 acts as a substrate for PBL in cytokinesis, compromising RHO1 function in the mesoderm does not block cell migration. These data suggest that the function of PBL in cell migration might be mediated through a pathway distinct from RHO1. This idea is supported by allele-specific differences in the expressivity of the cytokinesis and cell migration phenotypes of different pbl mutants. We show that PBL is autonomously required in the mesoderm for cell migration. Like HTL, PBL is required for early cell shape changes during mesoderm migration. Expression of a constitutively active form of HTL is unable to rescue the early cellular defects in pbl mutants, suggesting that PBL is required for the ability of HTL to trigger these cell shape changes. These results provide evidence for a novel function of the Rho-GEF PBL in HTL-dependent mesodermal cell migration.

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In Vivo Imaging Reveals Different Cellular Functions for FGF and Dpp Signaling in Tracheal Branching Morphogenesis

Cited by 148 publications

References 25 publications

VEGF and endothelial guidance in angiogenic sprouting

VEGF and endothelial guidance in angiogenic sprouting

Tracheal branching morphogenesis inDrosophila: new insights into cell behaviour and organ architecture

The RhoGEF Pebble is required for cell shape changes during cell migration triggered by theDrosophilaFGF receptor Heartless

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