mRNAs of serpentine and vermiform are detected in the developing tracheal system beginning at embryonic stage 12. Both genes are also expressed in the developing stomodeum beginning at stage 14 and in the epidermis at stage 16. Tracheal expression of both genes starts to fade at stage 15 and is no longer detected at stage 16 (Luschnig, 2006).
Antisera were generated against short synthetic peptides derived from the serp and verm coding sequences, respectively. Immunostaining and immunoblot analysis demonstrated that the anti-Serp and anti-Verm antisera do not cross-react with one another's proteins. Serp and Verm proteins are first detected in early stage-13 embryos in a punctate perinuclear distribution in tracheal cells. About 1 hr later, just before Dorsal trunk (DT) branches fuse, the two proteins begin to accumulate in the lumen of the DT. They appear first in the lumen of the most posterior DT segments and slightly later in more anterior DT segments. During stages 14 and 15, the proteins appear in the lumen of all of the other tracheal branches. Intracellular staining of Serp and Verm proteins persists through stage 15, but is no longer detected at stage 16 (Luschnig, 2006).
Chitin forms a cylinder inside the tracheal lumen, and this cylinder is first detected in the DT just before DT dilation and then expands as the lumen dilates. Luminal chitin is secreted hours before the chitinous tracheal procuticle forms at the end of embryogenesis, and it is degraded or expelled from the tracheal lumen when the tubes are mature and just before they fill with gas. The chitin cylinder has a slightly smaller diameter than that of the lumen, which is bounded by the apical surface of the tracheal epithelium. Strong staining of Serp and Verm protein colocalized with the chitin cylinder, whereas there was only weak staining in the small gap between the cylinder and the apical surface of DT cells. This contrasts with the distribution of another luminal antigen, 2A12, which was distributed throughout the entire luminal space including the gap (Luschnig, 2006).
The colocalization of Serp and Verm with the chitin cylinder, and the presence in each protein of a chitin binding domain (CBD), suggest that the proteins directly associate with the chitin cylinder. Two experiments support this. (1) The organized and regular distribution of Serp and Verm proteins in the lumen requires chitin. In embryos homozygous for kkv1 (a mutation in the chitin synthase I gene), which lack tracheal chitin, Serp and Verm proteins are still expressed and secreted into the lumen. However, the distribution of the proteins is altered -- they form irregular, amorphous masses in the lumen, as does 2A12 antigen. (2) The CBD is apparently sufficient for localization to the chitin cylinder. A transgene expressing just an N-terminal fragment of Serp including the CBD fused to GFP [Serp(CBD)-GFP showed the same colocalization with the chitin cylinder as endogenous Serp protein and full-length Serp-GFP. It is concluded that Serp and Verm proteins associate with the luminal chitinous matrix and that this association is likely to be mediated at least in part by the CBD (Luschnig, 2006).
Epithelial tubes are the functional units of many organs, but little is known about how tube sizes are established. Using the Drosophila tracheal system as a model, it has been shown that mutations in varicose (vari) cause tubes to become elongated without increasing cell number. This study shows how vari is required for accumulation of the tracheal size-control proteins Vermiform and Serpentine in the tracheal lumen. vari is an essential septate junction (SJ) gene encoding a membrane associated guanylate kinase (MAGUK). In vivo analyses of domains important for MAGUK scaffolding functions demonstrate that while the Vari HOOK domain is essential, the L27 domain is dispensable. Phylogenetic analyses reveal that Vari helps define a new MAGUK subgroup that includes mammalian PALS2. Importantly, both Vari and PALS2 are basolateral, and the interaction of Vari with the cell-adhesion protein Neurexin IV parallels the interaction of PALS2 and another cell-adhesion protein, Necl-2. Vari therefore bolsters the similarity between Drosophila and vertebrate epithelial basolateral regions, which had previously been limited to the common basolateral localization of Scrib, Dlg and Lgl, proteins required for epithelial polarization at the beginning of embryogenesis. However, by contrast to Scrib, Dlg and Lgl, Vari is not required for cell polarity but rather is part of a cell-adhesion complex. Thus, Vari fundamentally extends the similarity of Drosophila and vertebrate basolateral regions from sharing only polarity complexes to sharing both polarity and cell-adhesion complexes (Wu, 2007).
The function of organs such as the lung, kidney and vascular system depends on epithelial and endothelial tubes of specific sizes. However, the cell biological and molecular processes that control tube sizes are largely unknown. The Drosophila tracheal system is a network of ramifying epithelial tubes that serves as a combined pulmonary-vascular system to directly deliver oxygen to tissues. The comparative simplicity and genetic tractability of the tracheal system has made it one of the best models of tubular epithelial morphogenesis. The tracheal system develops from a series of sacs into a complex network of branches through a highly orchestrated series of cell migrations, cell shape changes and rearrangements of cell-cell junctions. An important element of these morphogenetic events is that changes in tube size occur reproducibly during specific developmental periods. Each tracheal branch has a specific size that results from the action of branch-specific signaling events that at least in some branches are known to act through transcription factors such as Spalt-Major (Spalt). At least one additional transcription factor, Grainyhead, is required to control tube length and apical cell surface in the major tracheal branches, but the transcriptional targets that more directly mediate these functions remain to be identified. Recent work by multiple groups has produced a basic molecular framework of the mechanisms that execute the size changes of 'tube expansion', a process that increases the diameter - but not the length - of the major tracheal tubes over a 2 hour period, and then gradually lengthens the tubes without changing their diameters. These tube size changes result from changes in cell shape and possibly cell size, but do not involve changes in cell number (Wu, 2007).
The tube expansion mechanism depends upon a fibrillar, chitin-based extracellular matrix that is assembled in the tracheal lumen at the beginning of the diameter dilation. As development progresses, chitin at the apical cell surface is organized into a highly patterned, multilayered cuticle. Lumenal chitin is eliminated before hatching. Defects in chitin synthesis or organization cause tracheal tube diameters to become either too large or too small, and tube lengths to become over-elongated. The exact role of the chitin-based matrix in controlling tracheal cell shape is unclear. Although the lumenal matrix and cuticle may serve as structural forms or 'mandrils' that mechanically shape the tracheal cells and tubes, an instructive or signaling role for the matrix is suggested by the observation that the organization of the βH-spectrin cytoskeleton is altered in chitin-synthetase mutants (Wu, 2007).
Beginning at stage 15, organization of the lumenal matrix requires the lumenal secretion of the putative chitin deacetylases, Vermiform (Verm) and Serpentine (Serp). In verm and serp mutants, the chitin-based matrix becomes disorganized and tracheal tubes become too long. Surprisingly, lumenal secretion of Verm requires a cell-cell junction termed the septate junction (SJ). Septate junctions are complex cell adhesion junctions that have at least 15 known components. These include transmembrane cell-adhesion proteins such as Neurexin IV (Nrx-IV; herein referred to as Nrx) and Neuroglian (Nrg), cytoplasmic proteins such as the FERM-domain protein Coracle (Cor; Cora - Flybase), the basal polarity proteins Scribbled (Scrib), Discs large (Dlg; Dlg1 -Flybase), and Lethal giant larvae (Lgl; L(2)gl - Flybase), and proteins with roles that remain to be determined, such as the Na+/K+-ATPase. Mutations in most known SJ components cause tracheal phenotypes indistinguishable from the verm mutant phenotype, consistent with the failure of Verm to be secreted into the tracheal lumen in the SJ mutants so far examined. Secretion of other apical lumenal markers appears normal in SJ mutants, indicating that Verm is secreted by a specialized pathway, the mechanism of which remains to be determined (Wu, 2007).
Although the role of SJs in lumenal (apical) secretion is not understood, other SJ functions are well defined. SJs have functional and molecular similarity to vertebrate tight junctions (TJs), in that both junctions require members of the claudin protein family to create the paracellular diffusion barriers between epithelial cells that are essential to the survival of multicellular animals. However, SJs are not simply the homologs of TJs, because there are significant ultrastructural, molecular and functional differences between SJ and TJs. For example, TJs are apical of adherens junctions (AJs) and contain conserved apical polarity complexes, while SJs are basal of AJs and contain the polarity proteins Scrib, Dlg and Lgl, which have vertebrate homologs that also localize basolaterally. Thus, in some respects SJs are more related to complexes found in the basolateral regions of vertebrate epithelial cells than to TJs (Wu, 2007).
Although Scrib, Dlg and Lgl establish and currently define the similarity between SJ and vertebrate basolateral regions, it is notable that these proteins are not representative of most SJ components. Drosophila Scrib, Dlg and Lgl are maternally contributed and constitute a distinct subgroup of proteins required for initial epithelial cell polarization during embryonic stages 5-8. By contrast, most SJ components are not maternally expressed, are not required for cell polarity and only function relatively late in development when SJs begin forming during stage 13. Whether the Scrib, Dlg and Lgl proteins nucleate SJ assembly, or whether the nascent SJ recruits and incorporates Scrib, Dlg and Lgl has not been determined. It also has not yet been determined how Scrib, Dlg and Lgl are localized to the basolateral membrane in either Drosophila or vertebrate epithelia. Thus the similarity between Drosophila SJ and vertebrate basolateral regions has been limited to polarity complexes, and has not extended to cell adhesion complexes (Wu, 2007).
This report shows that vari encodes a previously uncharacterized, membrane-associated, guanylate kinase (MAGUK) scaffolding protein that is required for SJ organization and directly binds the cell adhesion protein Neurexin IV. Importantly, Vari helps define a new subgroup of MAGUKs that includes vertebrate PALS2. Both Vari and PALS2 localize basolaterally in epithelial cells and both interact through a PDZ domain with a basolateral adhesion protein. Thus, Vari is the first late-expressed SJ component to have a vertebrate homolog, and together Vari and PALS2 extend the similarity of Drosophila and vertebrate basolateral regions from polarity complexes to adhesion complexes (Wu, 2007).
Vari was originally identified as a gene required for regulating the size of epithelial tubes. In vari mutants, tracheal tubes become too long without changes in tracheal cell number. This study shows that Vari encodes multiple isoforms of a MAGUK that helps define a new subgroup of MAGUKs. Vari functions in the assembly of the septate junctions and is required for the apical secretion of the protein Verm, which is thought to be responsible for modifying a chitin-based lumenal matrix. In vari and other SJ mutants, Verm is not secreted, the lumenal matrix becomes abnormal and tracheal tubes become elongated (Wu, 2007).
The protein-protein interaction domains present in Vari suggest it acts as a scaffolding protein that helps bring together different components of the SJ complex. This hypothesis is supported by GST-pull down assay results showing Vari's PDZ domain can directly bind the intracellular domain of Nrx, a transmembrane SJ adhesion protein. Binding of the Vari PDZ domain to Nrx would leave Vari's SH3, GUK and predicted C-terminal PDZ-binding motif available to anchor other SJ components to the membrane, or to bring together different transmembrane SJ components. One model is that Vari may help bring the Dlg-Scib complex to the membrane through interfolding of the Vari and Dlg SH3 domains, which is made possible by the unique HOOK domain insert in the MAGUK SH3 domains. Whether or not Vari anchors the Dlg complex to the rest of the SJ, genetic evidence indicates that Vari has functions beyond simply bridging between transmembrane Nrx and intracellular SJ complexes, because vari mutations can strongly enhance the phenotypes caused by mutations in the Drosophila claudin sinuous, whereas nrx mutations do not enhance sinuous mutations (Wu, 2007).
By itself, the finding that Vari encodes a MAGUK was not unexpected, as many MAGUKs are associated with cell-cell junctions. However, it is significant that Vari helps define a new subgroup of MAGUKs that includes mammalian PALS2, because Vari and PALS2 both localize basolaterally and bind the C-termini of basolateral cell adhesion proteins. Thus, Vari and PALS2 bolster the similarity between Drosophila and vertebrate epithelial basolateral regions that was first evidenced by the common basolateral localization of the Scrib, Dlg and Lgl early polarity proteins. However, by contrast to the polarity proteins, Vari is not required for cell polarity but rather is expressed late in embryonic development and is part of a cell-adhesion complex. Thus, Vari fundamentally extends the similarity of Drosophila and vertebrate basolateral regions from containing only conserved polarity complexes to containing both conserved polarity and cell-adhesion complexes (Wu, 2007).
The finding of more extensive similarity between SJ and vertebrate basolateral regions suggests that continued study of Drosophila SJs will provide insight into vertebrate epithelial basolateral regions. Further, these results support the idea that during evolution there has been conservation of different junctional functions, such as forming paracellular barriers and anchoring of polarity complexes. However, the comparison of TJs and SJs also makes it clear that there has been limited conservation of which particular functions have assorted to different junctions. An attractive explanation for these somewhat contradictory observations is that junctional functions are modular, and that the disparate junctions in different species represent alternative combinations of functional modules. For example, Drosophila SJs could be considered a combination of the claudin-based paracellular-barrier function and the basolateral polarity proteins Dlg, Scrib and Lgl. Alternatively, vertebrate TJs could be considered a combination of the claudin-based paracellular-barrier function and the apical polarity complexes of Crbs-Baz and Sdt-aPKC-Par-6. Thus, when comparing junctions between species, it is likely to be more useful to compare specific junctional functions, such as molecular details of polarity or barrier functions, than to attempt to directly compare junctions in their entirety (Wu, 2007).
If complex junctions such as TJs and SJs are comprised of functional modules, one would expect that these junctions should contain distinct molecular subcomplexes that mediate distinct functions. Consistent with this proposal, extensive work by many labs has shown that the polarity proteins of Crb-Sdt and Baz-cdc42-aPKC form specific complexes. Claudin proteins appear to be part of a 'barrier complex' because claudins are required for and co-localize with the paracellular barrier in both Drosophila and vertebrates. Functional demonstration of the independence of the barrier and polarity complexes in both species is provided by the observations that cell polarity is not affected by selective disruption of the barrier complex in either mammals by knockdown of ZO-1 and ZO-2, or in Drosophila by mutations in claudin genes. The Vari/PALS2 proteins could play a pivotal role in allowing cytoplasmic subcomplexes to associate different adhesion-junctional complexes, either in different cell types or during evolution, because changing which adhesion complex Vari or PALS2 associate with could be as simple as changing the four amino acid PDZ-binding motifs of one or a few transmembrane proteins. It seems likely that evolving a few unstructured amino acids would be significantly easier than evolving three-dimensional binding surfaces. Thus, Vari and its homologs could provide crucial (but malleable) links between conserved intracellular complexes and the divergent transmembrane junctional complexes found across the animal kingdom (Wu, 2007).
Many organs contain epithelial tubes that transport gases or liquids. Proper tube size and shape is crucial for organ function, but the mechanisms controlling tube diameter and length are poorly understood. Recent studies of tracheal (respiratory) tube morphogenesis in Drosophila show that chitin synthesis genes produce an expanding chitin cylinder in the apical (luminal) extracellular matrix (ECM) that coordinates the dilation of the surrounding epithelium (Tonning, 2005; Devine, 2005). This study describes two genes involved in chitin modification, serpentine (serp) and vermiform (verm), mutations that cause excessively long and tortuous tracheal tubes. The genes encode similar proteins with an LDL-receptor ligand binding motif and chitin binding and deacetylation domains. Both proteins are expressed and secreted during tube expansion and localize throughout the lumen in a chitin-dependent manner. Unlike previously characterized chitin pathway genes, serp and verm are not required for chitin synthesis or secretion but rather for its normal fibrillar structure. The mutations also affect structural properties of another chitinous matrix, epidermal cuticle. This work demonstrates that chitin and the matrix proteins Serp and Verm limit tube elongation, and it suggests that tube length is controlled independently of diameter by modulating physical properties of the chitin ECM, presumably by N-deacetylation of chitin and conversion to chitosan (Luschnig, 2006).
Genetic pathways controlling branching morphogenesis and cell-type diversification of the Drosophila tracheal system have been characterized. However, it is not known how tracheal cells measure, regulate, and maintain distinct sizes and shapes of epithelial tubes. Genetic screens have identified genes that influence the diameter, length, and shape of tracheal tubes (Beitel, 2000). Many of these encode components of septate junctions, the insect cognate of vertebrate tight junctions. Recently, genes involved in the synthesis of a cylindrical chitin matrix secreted by tracheal cells prior to cuticle formation were identified and shown to play an essential role in controlling tracheal tube diameter (Devine, 2005; Tonning, 2005). This study described the identification and characterization of two genes that encode apical extracellular matrix (ECM) proteins that modify the structure of the chitin matrix and regulate tracheal tube length (Luschnig, 2006).
In a genomic search for genes regulated by the transcription factor Ribbon, a nuclear BTB/POZ domain protein that promotes movement and morphogenesis of the apical surface of the tracheal epithelium, two adjacent genes were identified at cytological position 76C1-2 (CG32209 and CG8756) that encode structurally related tracheal matrix proteins. The genes are expressed in indistinguishable patterns. mRNAs of both genes were detected in the developing tracheal system beginning at embryonic stage 12, just after Ribbon protein is detected, and expression of both genes was reduced in ribbon null mutants as determined by in situ hybridization and DNA microarray analysis (6-fold reduction of CG32209 and 5-fold reduction of CG8756). The genes were named serpentine (serp; CG32209) and vermiform (verm; CG8756) on the basis of their elongated and convoluted tracheal phenotypes described below (Luschnig, 2006).
To analyze the developmental functions of the genes, putative null mutations in each gene were identified. A P element insertion in CG8756 (vermKG) is embryonic lethal when homozygous. Excision of the transposon restored viability of the parental chromosome in 9 of 13 excision events, indicating that the lethality is due to the P element. One imprecise excision, vermex7, removed the transposon and 556 bp of flanking genomic DNA, including the first coding exon of CG8756, which is common to all known splice variants and includes the start codon and signal peptide, suggesting that vermex7 is a null allele. The parental P element insertion also appears to be a null allele because Verm protein expression was not detected by immunostaining and its phenotype was indistinguishable from vermex7. serpRB is an insertion in CG32209 of a PiggyBac transposon designed to disrupt mRNA splicing. It eliminated expression of Serp protein and behaved as a null allele in genetic tests (Luschnig, 2006).
Tracheal development in serp and verm mutants was analyzed with specific markers for tracheal cells and the tracheal lumen. No defects were detected early in tracheal development in any of the homozygous mutants analyzed. Dorsal trunk (DT) branches budded, fused, and dilated normally. However, during stage 15 (~13 hr after egg lay at 25°C) in both serp and verm homozygous embryos, the DT began to elongate inappropriately and became convoluted. The effects are more dramatic in homozygous serpRB vermKG double mutants: The DT began to elongate excessively at stage 15 and by stage 16 (15 hr AEL) was 40% longer than normal and highly convoluted. Similar effects were observed in other branches including the transverse connective (TC), although the effects were not as pronounced in smaller-caliber branches, such as the dorsal branch (DB). The phenotype of hemizygous serpRB vermKG embryos (in trans to Df(3L)Exel6135 that removes serp and verm) was indistinguishable from homozygous serpRB vermKG embryos. In contrast to the dramatic effects of the mutations on tracheal tube length and shape, there was little or no effect of the mutations on the diameter of the tubes. The DT showed its characteristic posterior to anterior taper, and was of normal caliber except for slight constrictions that were occasionally observed near DT fusion joints in serpRB vermKG double mutants. It is concluded that serp and verm are required to restrict tracheal tube length. This distinguishes them from a second class of tracheal-tube morphogenesis genes that are required to establish and maintain correct tube diameter and are involved in chitin synthesis (e.g., kkv) (Luschnig, 2006).
In serpRB vermKG double mutants, the tracheal lumen is excessively long and forms dramatic corkscrew-like twists. Immunostaining for Crumbs (Crb) protein, which localizes to the apical marginal zone of epithelial cells, showed that the apical tracheal surface is similarly elongated and convoluted in the mutants. However, the basal (outer) surface of the tracheal epithelium did not appear to follow the convoluted path of the lumen and apical surface. This suggests that serp and verm act to selectively restrict expansion of the lumen and apical surface of the tracheal epithelium. A similar mutant phenotype has been described for grainyhead (grh), which encodes a transcription factor proposed to restrict tracheal tube elongation through transcriptional regulation of apical matrix genes (Hemphala, 2003). Serp and Verm proteins are still expressed in grhIM mutant embryos, suggesting that serp and verm are not critical targets of Grh (Luschnig, 2006).
The selective effect of serp and verm mutations on the apical surface and the length and convolution of tracheal tubes also resembles the tube-morphogenesis defect of mutants in megatrachea and other genes that encode components of septate junctions (SJs). Although the mechanism by which SJs influence tube length is not understood, all of the SJ mutants that have been tested affect the pericellular-diffusion barrier function of tracheae and other epithelia. To determine whether tracheal barrier function is compromised in serp verm double mutants, rhodamine-labeled dextran (MW ~10 kDa) was injected into the body cavity of mutant and control embryos and its distribution was analyzed 25 min later. In megaG0012 and other SJ mutants, dextran passes through the tracheal epithelium and into the lumen. By contrast, in serp verm double mutants, dextran is excluded from the tracheal lumen, as it is in the wild-type control. It is concluded that epithelial barrier function is grossly intact in the serp verm double mutant and that the tube-morphogenesis defect does not result from disruption of SJ barrier function (Luschnig, 2006).
Whether serp and verm mutations affect the synthesis or structure of chitin was investigated. There was no detectable effect in serp verm double-mutant embryos on the level of luminal chitin staining, demonstrating that serp and verm function is not required for the synthesis, secretion, or luminal accumulation of chitin. Likewise, the secretion and luminal accumulation of 2A12 antigen and the zona pellucida protein PioPio were not disrupted in serp verm mutants. However, the morphology and structure of the luminal chitin cylinder was altered in serp verm mutant embryos. High-resolution confocal imaging of luminal chitin stained with a fluorescently labeled chitin binding protein revealed that the chitin cylinder in wild-type embryos is fibrous and has a smooth surface. By contrast, in serp verm mutants, the fibrous structure of the chitin cylinder is abolished and the surface of the cylinder is irregular. Also, the small gap between the chitin cylinder and the apical epithelial surface is absent. Morphological defects in chitin structure are apparent in serp verm mutants by stage 14, several hours before the elongated-tube phenotype begins to manifest. This implies that the defects in chitin structure are not a secondary consequence of the disruption in tube morphology, and support an alternative model in which a serp- and verm-dependent alteration in chitin structure influences tube length. serp and verm are also expressed in epidermal cells, and the mutations affect body shape, presumably by altering the structure and rigidity of epidermal cuticle, another chitinous matrix (Luschnig, 2006).
These findings in the Drosophila tracheal system could have implications for the mechanisms of tube size and shape regulation in other tubular epithelial organs, including those of vertebrates. For example, blood vessels grown in vitro from human endothelial cells contain a fibrous luminal matrix that is of unknown composition and function and has been postulated to play a role in tube morphogenesis. Although there are many molecular differences among the luminal ECMs of blood vessels, tracheal tubes, and other tubular organs in animals, they could act similarly to regulate and maintain the diameter, length, and shape of the surrounding tubes. Indeed, synthetic mandrils are used in this way in blood-vessel engineering. It will be important to identify and characterize the components of the luminal matrices of blood vessels and other types of tubes, and to determine whether dynamic and specific changes in the structure and physical properties of these matrices are used to regulate tube size and shape in vivo, as proposed for Drosophila tracheal tubes (Luschnig, 2006).
Reference names in red indicate recommended papers.
Beitel, G. J. and Krasnow, M. A. (2000). Genetic control of epithelial tube size in the Drosophila tracheal system. Development 127(15): 3271-82. 10887083
Devine, W. P., Lubarsky, B., Shaw, K., Luschnig, S., Messina, L. and Krasnow, M. A. (2005). Requirement for chitin biosynthesis in epithelial tube morphogenesis. Proc. Natl. Acad. Sci. 102(47): 17014-9. 16287975
Hemphala, J., Uv, A., Cantera, R., Bray, S. and Samakovlis, C. (2003). Grainy head controls apical membrane growth and tube elongation in response to Branchless/FGF signalling. Development 130(2): 249-58. 12466193
Luschnig, S., Batz, T., Armbruster, K. and Krasnow, M. A. (2006). serpentine and vermiform encode matrix proteins with chitin binding and deacetylation domains that limit tracheal tube length in Drosophila. Curr. Biol. 16(2): 186-94. 16431371
Magkrioti, C. K., et al. (2004). cuticleDB: a relational database of Arthropod cuticular proteins. BMC Bioinformatics 5: 138. 15453918
Merzendorfer, H. and Zimoch, L. (2003). Chitin metabolism in insects: structure, function and regulation of chitin synthases and chitinases. J. Exp. Biol. 206(Pt 24): 4393-412. 14610026
Ostrowski, S., Dierick, H. A. and Bejsovec, A. (2002). Genetic control of cuticle formation during embryonic development of Drosophila melanogaster. Genetics 161(1): 171-82. 12019232
Tonning, A., Hemphala, J., Tang, E., Nannmark, U., Samakovlis, C. and Uv, A. (2005). A transient luminal chitinous matrix is required to model epithelial tube diameter in the Drosophila trachea. Dev. Cell 9(3): 423-30. 16139230
Tsigos, I., Martinou, A., Kafetzopoulos, D. and Bouriotis, B. (2000). Chitin deacetylases: New, versatile tools in biotechnology, Trends Biotechnol. 18: 305-312. 10856926
Wang, S., Jayaram, S. A., Hemphala, J., Senti, K. A., Tsarouhas, V., Jin, H. and Samakovlis, C. (2006). Septate-junction-dependent luminal deposition of chitin deacetylases restricts tube elongation in the Drosophila trachea. Curr. Biol. 16(2): 180-5. 16431370
Wu, V. M., et al. (2007). Drosophila Varicose, a member of a new subgroup of basolateral MAGUKs, is required for septate junctions and tracheal morphogenesis. Development 134(5): 999-1009. PubMed Citation: 17267446
date revised: 20 December 2009
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