Drosophila Dumpy is a gigantic extracellular protein required to maintain tension at epidermal–cuticle attachment sites

Mb, Wilkin; Mn, Becker; Mulvey, D.; Phan, Isabelle; Chao, Anna T.; Cooper, Kristen B.; Chung, Henry; Id, Campbell; M, Baron; MacIntyre, Ross J.

doi:10.1016/s0960-9822(00)00482-6

Cited by 143 publications

(150 citation statements)

References 36 publications

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“…Both Pio and Dp proteins contain a zona pellucida (ZP) domain and are apically secreted into the luminal space of the developing tracheal system. Dp, in addition to its ZP domain, contains hundreds of Egf repeats interspersed with 21-residue-long, so-called, Dumpy (DPY) modules, and, at roughly 21,000 amino acids, it is the largest known Drosophila protein (Wilkin et al, 2000). As ZP domains form fibrillar structures (reviewed by Jovine et al, 2005), these studies strongly suggest that an apical extracellular matrix (ECM) that contains Pio and Dp provides a structural meshwork in the luminal space, around which cell rearrangements can take place in an ordered fashion and without losing interconnections.…”

Section: The Role Of Cell Intercalationmentioning

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 Intercalationmentioning

confidence: 99%

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

2008

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“…Recently, two interesting molecules residing in the luminal ECM of tracheae have been characterized, dumpy (39) and piopio (40). They are involved in maintenance and formation of the tracheal tube.…”

Section: Silencing Of Fat-like Transcript Impairs Tubular Tissue Formmentioning

confidence: 99%

“…In addition, they also showed adhesive properties in other tissues such as the wing (41,42). Both proteins are secreted apically, and it has been proposed that Dumpy, through its enormous size of 800 nm, acts as a ruler setting the diameter of secondary branches (39). It is possible that these molecules interact with Ftl directly or through the ECM.…”

Section: Silencing Of Fat-like Transcript Impairs Tubular Tissue Formmentioning

confidence: 99%

The fat-like Gene of Drosophila Is the True Orthologue of Vertebrate Fat Cadherins and Is Involved in the Formation of Tubular Organs

Castillejo-López¹,

Arias²,

Baumgärtner³

2004

Journal of Biological Chemistry

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Fat cadherins constitute a subclass of the large cadherin family characterized by the presence of 34 cadherin motifs. To date, three mammalian Fat cadherins have been described; however, only limited information is known about the function of these molecules. In this paper, we describe the second fat cadherin in Drosophila, fat-like (ftl). We show that ftl is the true orthologue of vertebrate fat-like genes, whereas the previously characterized tumor suppressor cadherin, fat, is more distantly related as compared with ftl. Ftl is a large molecule of 4705 amino acids. It is expressed apically in luminal tissues such as trachea, salivary glands, proventriculus, and hindgut. Silencing of ftl results in the collapse of tracheal epithelia giving rise to breaks, deletions, and sac-like structures. Other tubular organs such as proventriculus, salivary glands, and hindgut are also malformed or missing. These data suggest that Ftl is required for morphogenesis and maintenance of tubular structures of ectodermal origin and underline its similarity in function to a reported lethal mouse knock-out of fat1 where glomerular epithelial processes collapse. Based on our results, we propose a model where Ftl acts as a spacer to keep tubular epithelia apart rather than the previously described adhesive properties of the cadherin superfamily.

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“…The dp locus spans over 100 kb, encoding a 2.5 MDa modular extracellular matrix protein with 308 EGF modules and 185 DPY modules required for the anchoring of epidermal tissue to the fly cuticle (WILKIN et al 2000). The 79 dp coding exons are in 53 MPOs, and the region from exon 37 to 70 has 34 coding exons in 13 MPOs (Supplemental Figure 1).…”

Section: Supplemental Textmentioning

confidence: 99%

Probing the Boundaries of Orthology: The Unanticipated Rapid Evolution ofDrosophila centrosomin

Eisman

2013

Genetics

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The rapid evolution of essential developmental genes and their protein products is both intriguing and problematic. The rapid evolution of gene products with simple protein folds and a lack of well-characterized functional domains typically result in a low discovery rate of orthologous genes. Additionally, in the absence of orthologs it is difficult to study the processes and mechanisms underlying rapid evolution. In this study, we have investigated the rapid evolution of centrosomin (cnn), an essential gene encoding centrosomal protein isoforms required during syncytial development in Drosophila melanogaster. Until recently the rapid divergence of cnn made identification of orthologs difficult and questionable because Cnn violates many of the assumptions underlying models for protein evolution. To overcome these limitations, we have identified a group of insect orthologs and present conserved features likely to be required for the functions attributed to cnn in D. melanogaster. We also show that the rapid divergence of Cnn isoforms is apparently due to frequent coding sequence indels and an accelerated rate of intronic additions and eliminations. These changes appear to be buffered by multi-exon and multi-reading frame maximum potential ORFs, simple protein folds, and the splicing machinery. These buffering features also occur in other genes in Drosophila and may help prevent potentially deleterious mutations due to indels in genes with large coding exons and exon-dense regions separated by small introns. This work promises to be useful for future investigations of cnn and potentially other rapidly evolving genes and proteins.A S the genomic era advances, molecular biology has shifted from single-gene studies to global analyses of genomes from a broad phylogenetic range of organisms. For single-gene and global studies, a critical first step for molecular biologists is the accurate identification of orthologous genes. The concept of orthology was introduced by Fitch to differentiate between orthologous genes, which have a oneto-one relationship between species, and paralogous genes, which result from a duplication event of the original ortholog within a species (Fitch 1970(Fitch , 2000. Because orthologs are often more closely related than paralogs, it is generally assumed that gene function is likely to be conserved. Since the functional annotation of uncharacterized genomes is generally computationally based on overall sequence identity with known genes from model organisms, it is essential for orthology assignments to be accurate (Hulsen et al. 2006). The importance of orthology is made evident both by the number of databases reporting orthologous gene sets and by the number of terms introduced to describe relational subcategories in the time since Fitch initially introduced the concept of orthologous and paralogous gene relationships.Since orthologous genes are related by descent and orthology is based on sequence homology and phylogeny, the process of identification should be relatively simple. Thi...

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Drosophila Dumpy is a gigantic extracellular protein required to maintain tension at epidermal–cuticle attachment sites

Cited by 143 publications

References 36 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 fat-like Gene of Drosophila Is the True Orthologue of Vertebrate Fat Cadherins and Is Involved in the Formation of Tubular Organs

Probing the Boundaries of Orthology: The Unanticipated Rapid Evolution ofDrosophila centrosomin

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