FGF Is an Essential Mitogen and Chemoattractant for the Air Sacs of the Drosophila Tracheal System

Sato, Makoto; Kornberg, Thomas B.

doi:10.1016/s1534-5807(02)00202-2

Cited by 212 publications

(319 citation statements)

References 35 publications

Supporting

Mentioning

307

Contrasting

Order By: Relevance

“…Our findings, thus, show that MMP expression in PS cells drives degradation of the BM of both PS cells and the apposed larval epidermis, which is essential for this invasive developmental process. Another developmental invasion process is the penetration of the wing disc by the trachea (33). It would be interesting to learn whether a similar mechanism is involved.…”

Section: Discussionmentioning

confidence: 99%

Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion

Srivastava

Pastor-Pareja

Igaki

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

181

240

View full text Add to dashboard Cite

Organ and tissue integrity is often maintained in animals by a specialized extracellular matrix structure called the basement membrane (BM). Accumulated evidence indicates that BM remodeling occurs during development and tumor invasion. Although the BM organizes and functions at the organ level, most past studies have explored its biochemical and in vitro properties. In this study, we monitor the BM in vivo during developmental tissue invasion for disc eversion and tumor invasion in Drosophila and modulate BM integrity with genetic alterations affecting either the whole organism or the targeted discs or tumors. We observe that the degradation of BM by the discs or the tumors is an early event during invasion processes and that preventing BM degradation completely blocks both tissue and tumor invasion, indicating that modulation of BM is essential for developmental and tumor invasion. Furthermore, elements of the invasion machinery, including JNK-induced matrix metalloproteinase (MMP) expression, are shared by both disc eversion and tumor invasion processes. Moreover, we show that although expression of MMP inhibitor, TIMP, is sufficient to halt developmental invasion, inhibition of proteases by both TIMP and RECK are required to block tumor invasion. These data suggest that tumor cells have a more robust invasion mechanism and could acquire metastatic behavior by co-opting developmental invasion programs. This type of co-option may be a general feature contributing to the progression of tumors. Finally, although past efforts using MMP inhibitors have not yielded much success, our results strongly argue that BM modulation could be a critical target for cancer therapy.developmental invasion ͉ JNK signaling ͉ tumor metastasis ͉ matrix metalloproteinase

show abstract

Section: Discussionmentioning

confidence: 99%

Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion

Srivastava

Pastor-Pareja

Igaki

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

181

240

View full text Add to dashboard Cite

show abstract

“…In an earlier pioneering study, Sato and Kornberg showed that the formation of the primordia of the air sac of the dorsal thorax of the adult fly develops during the third instar larval stage under the control of Bnl/Fgf (Sato and Kornberg, 2002). Tracheal cells in close vicinity to Bnl-secreting cells in the wing imaginal disc start to proliferate and migrate towards Bnl-expressing cells.…”

Section: The Role Of Cell Migrationmentioning

confidence: 99%

“…This is mostly because large maternal stores exist of many of the important components of this process, which hinder genetic approaches to identifying these components in embryos. However, many maternally provided transcripts and proteins have been used up by the third instar larval stages, and this has allowed researchers to use genetic mosaic analysis to investigate whether a given gene is specifically required for air sac primordia formation in an otherwise heterozygous animal, as discussed in more detail below.In an earlier pioneering study, Sato and Kornberg showed that the formation of the primordia of the air sac of the dorsal thorax of the adult fly develops during the third instar larval stage under the control of Bnl/Fgf (Sato and Kornberg, 2002). Tracheal cells in close vicinity to Bnl-secreting cells in the wing imaginal disc start to proliferate and migrate towards Bnl-expressing cells.…”

mentioning

confidence: 99%

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

2008

View full text Add to dashboard Cite

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)....

show abstract

“…Fibroblast-growth-factor receptors (FGFR) have been implicated in early steps of directional cell migration in development (Szebenyi and Fallon, 1999). One function of FGFRs in vivo is to recognize chemotactic gradients of FGF that direct cell migration in the embryo (Sato and Kornberg, 2002;Sutherland et al, 1996;Yang et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2004

View full text Add to dashboard Cite

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.

show abstract

FGF Is an Essential Mitogen and Chemoattractant for the Air Sacs of the Drosophila Tracheal System

Cited by 212 publications

References 35 publications

Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion

Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion

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

Contact Info

Product

Resources

About