The Drosophila Protein Dof Is Specifically Required for FGF Signaling

Vincent, Stéphane; Wilson, Robert; Coelho, Carmen M. A.; Affolter, Markus; Leptin, Maria

doi:10.1016/s1097-2765(00)80151-3

Cited by 158 publications

(174 citation statements)

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“…Tracheal cells express a Fgf receptor, encoded by the breathless (btl) locus (Klambt et al, 1992), as well as a Fgf-specific signalling adaptor protein encoded by downstreamof-Fgfr (dof; also known as stumps) (Vincent et al, 1998;Imam et al, 1999;Petit et al, 2004;Wilson et al, 2004). As for rho and cvc expression (discussed above), btl and dof expression also require the Trh transcription factor, and the accumulation of btl and dof clearly distinguishes tracheal cells from neighbouring, non-tracheal, cells and prepares them for the branching process.…”

Section: The Role Of Cell Migrationmentioning

confidence: 99%

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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Section: The Role Of Cell Migrationmentioning

confidence: 99%

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

2008

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“…Mesoderm migration depends on the mesoderm-specific expression and activity of both the HTL receptor and its putative cytoplasmic adaptor DOF (Beiman et al, 1996;Gisselbrecht et al, 1996;Michelson et al, 1998a;Shishido et al, 1993;Vincent et al, 1998). By contrast, pbl is expressed in all cells of the embryo and is required in all cells for cytokinesis in postblastoderm embryos (Hime and Saint, 1992;Lehner, 1992;Prokopenko et al, 2000a).…”

Section: Requirement Of Pbl For Cell Migration Is Specific For Mesodementioning

confidence: 99%

“…Molecular and genetic epistasis has shown that HTL activates the conserved Ras/Raf/MAP kinase pathway during mesoderm migration and differentiation (Gabay et al, 1997;Michelson et al, 1998a;Michelson et al, 1998b;Vincent et al, 1998). To assess the function of PBL in HTL-dependent migration, we asked whether pbl is required for the activation of downstream components of the HTL pathway by measuring MAP kinase activation in pbl mutants.…”

Section: Pbl Activity Is Required For Htl Function In Triggering Cellmentioning

confidence: 99%

“…The signal transduction pathway downstream of HTL involves the product of the downstream of FGF (dof; stumpsFlyBase) gene (Imam et al, 1999;Michelson et al, 1998a;Vincent et al, 1998). Genetic experiments suggest that DOF functions as adaptor protein and operates downstream of the receptor and upstream of signals triggered by RAS1.…”

Section: Introductionmentioning

confidence: 99%

“…Genetic experiments suggest that DOF functions as adaptor protein and operates downstream of the receptor and upstream of signals triggered by RAS1. Furthermore, activation of MAP kinase was observed in a subgroup of migrating mesoderm cells and was shown to depend on HTL and DOF function (Gabay et al, 1997;Vincent et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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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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Suppression of glioblastoma cell growth following antisense oligonucleotide-mediated inhibition of fibroblast growth factor receptor expression

Yamada

Yamaguchi

Brown³

et al. 1999

Glia

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The Drosophila Protein Dof Is Specifically Required for FGF Signaling

Cited by 158 publications

References 46 publications

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

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

Suppression of glioblastoma cell growth following antisense oligonucleotide-mediated inhibition of fibroblast growth factor receptor expression

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