polychaetoid

DEVELOPMENTAL BIOLOGY

See the embryonic expression pattern of pyd at the Berkeley Drosophila Genome Project Patterns of Gene Expression Site.

Polychaetoid protein is localized at the cell-cell junction. Observation of the presumptive wing blade region of the wing imaginal disc reveals that Pyd has a more basal distribution compared with Shotgun (Takahisa, 1996). Pyd colocalizes with the scaffolding protein Canoe. In the cellular blastoderm (stage 5), the Cno protein is distributed diffusely in the cytoplasm, with significant accumulation at the apical surface. The cytoplasmic staining decreases before gastrulation. In stage 13 embryos undergoing germ-band retraction, marked accumulation of Cno is observed in the amnioserosa, with persistent expression of Cno in the lateral epidermis. The intense staining of the amnioserosa and the apposed edges of the lateral epidermis continues during dorsal closure. At this stage of embryogenesis, the trachea in each segment begins to elongate laterally to form the tracheal system across the segments. In addition, Cno is localized in Malpighian tubules, hindgut and the central nervous system. The tissue localization of Pyd is remarkably similar to that of Cno. It is present in the cytoplasm in the blastoderm stage embryo. In the later stages, Pyd is exclusively localized to cell boundaries. The epidermis, amnioserosa, the margin of the closing epidermis, the tracheal system, the Malpighian tubes, the hindgut and the CNS all express Pyd at high levels (Takahashi, 1998).

Ectodermal epithelium was examined for Pyd and Cno colocalization. The two proteins partially colocalize: Pyd expression is more widespread than Cno expression. The domain of Cno expression and that of Fas III expression are mutally exclusive, whereas the distributions of Arm and Drosophila alpha-catenin coincide with that of Cno. In contrast, Pyd is expressed in areas at which Fas III is localized. Fas III distribution is known to be restricted to septate junctions, and Drosophila alpha-catenin and Armadillo are confined to adherens junctions. Cno colocalizes with Arm but not with Fas III in the embryonic epidermis. Thus the results indicate that Pyd is present at both the septate and adherens junctions while Cno exists predominantly at adherens junctions (Takahashi, 1998).

To examine the Cortactin cellular localization, Cortactin was immunostained in epithelial cells of imaginal discs. The typical honeycomb-like images indicate that the protein distributes in a cell-cell contact-associated manner. To clarify the subcellular localization, the double stainings of Cortactin with Pyd, F-actin, and DE-cadherin (Shotgun) were conducted using a laser-scanning confocal microscope. DE-cadherin is a component of the adherens junction and localizes at the apicolateral region of epithelial cell junctions. The distribution of Pyd partially overlaps with that of DE-cadherin and extends to the slightly basal region, corresponding to the site of the septate junction. Colocalization of Cortactin, Pyd, and DE-cadherin is evident, while the staining area of Cortactin in the periplasm seemed slightly broader than that of either Pyd or DE-cadherin. Colocalization of Cortactin and F-actin in a periplasmic region is also observed. Regarding the apical-basal axis, the distribution of Cortactin extends from the basal half side of the adherens junction to the more baso-lateral region (Katsube, 1998).

Polychaetoid is required for dorsal closure of the embryo, sensory organ patterning, and cell fate specification in the developing eye. pyd is alternatively spliced resulting in two isoforms that differ by the presence or absence of exon 6. To determine the role of alternative splicing in Pyd function, antibodies specific for each isoform were generated. The exon 6⁺ form of Pyd is localized at adherens junctions of embryonic and imaginal epithelia, while the exon 6^- form is distributed broadly along the lateral membrane. These results suggest that localization of Pyd is controlled by alternative splicing and raises the possibility that exon 6 represents a distinct protein-protein interaction domain (Wei, 2001).

The temporal expression pattern of the two alternatively spliced pyd transcripts was determined by performing stage-specific RT-PCR, with the primers ex5-5' and ex7-3', using samples from 0-2, 2-4, 4-6, 6-8, and 8-24 h embryos, L3 larvae, early pupae and adults. The pyd6¹ form is present at all stages examined. However, transcripts at 0-2 h of embryogenesis represent both maternal and zygotic gene expression. RT-PCR with RNA isolated from unfertilized eggs demonstrates that the pyd6⁺ transcript is expressed maternally. The pyd6^- form is detected in 8-24 h embryos, L3 larvae, pupae and adults but the amount of PCR product is always less than that of the pyd6⁺ form. To determine more precisely when the pyd6^- transcript can first be detected, RT-PCR experiments with 8-12, 12-16, and 16-24 h embryos were conducted. The transcript is present at 8-12 h of embryogenesis, but the amount of PCR product is extremely low compared to the level of pyd6⁺ at the same stage. The level of the pyd6^- product increases at later developmental stages (late embryonic, L3, pupae, and adult) and the relative expression level of the two isoforms remains quite constant at these stages. Given that the same primers are used to detect both the 6⁺ and 6^- forms, and that the 6^- product is smaller than the 6⁺ product, it is thought that the consistently lower levels of the 6^- product are likely to reflect lower levels of expression of the 6^- isoform of the pyd transcript (Wei, 2001).

Cells are connected to neighboring cells and to the extracellular matrix by specialized junctions. In invertebrates, cell-to-cell junctions include adherens, septate and gap junctions. Note that the septate junction, which is thought to be functionally similar to the vertebrate tight junction, is basal to the adherens junctions. To determine the cell junction localization of Pyd proteins a series of immunofluorescent labeling experiments was performed in conjunction with specific cell junction markers (Wei, 2001).

The Drosophila wing disc is a monolayer of epithelial cells connected by adherens and septate junctions. Double labeling of wing discs with anti-Pyd (6⁺ and 6^- forms, respectively) and antibodies against septate junction proteins, Dlg or Coracle (Cor) shows that the 6⁺ form is apical to Dlg and Cor, suggesting that it is localized apically to septate junctions. The 6^- form is distributed more broadly since anti- Pyd 6^- staining is detected both apically and basally to Dlg and Cor (Wei, 2001).

Armadillo and E-cadherin are located at adherens junctions. Double labeling of wing discs was performed with antibody against E-cadherin (Shotgun) or Armadillo, and antibodies against the Pyd 6⁺ or Pyd 6^- isoforms. The Pyd 6⁺ isoform demonstrates co-localization with Shotgun and Arm, suggesting that Pyd 6⁺ is localized at adherens junctions. However, antibody staining of the Pyd 6^- isoform and Arm shows slight displacement of Pyd 6^- from the adherens junctions and its extension to a more basal region. These results suggest that the Pyd 6^- form is localized broadly around the cell membrane in imaginal discs. Results from double staining of the ectodermal epithelia of stage 11-14 embryos with antibodies against Pyd 6⁺ and Shotgun or antibodies against Pyd 6^- and Arm also support the above observations (Wei, 2001).

Expression of pyd6⁺ cDNA from a heat shock promoter can rescue the lethality of a pyd null mutation (pyd^C5) and also greatly suppresses the extra bristle phenotype of pyd^C5/pyd^J14 flies. The following experiments were carried out to study the role pyd6^- plays in SOP specification. The pyd6^- cDNA was inserted in the transformation vector CaSpeR under the control of the hsp70 promoter, and transgenic lines were generated. Flies were subjected to a heat shock regime. The experimental conditions were the same as those used for rescue of pyd^C5 lethality by the pyd6⁺ cDNA. Progeny were collected in vials and exposed repeatedly to a 37°C water bath for 1 h every 12 h from early embryogenesis (about 4-8 h after the eggs were laid) to the mid-pupal stage. Parents were heat-shocked at 37°C for 1 h and allowed to recover at 25°C for 1 h before collecting eggs, or remained continuously at 25°C (no heat shock). pyd 6^- does not rescue the lethal phenotype of pyd^C5. However, overexpression of pyd 6^- cDNA does significantly reduce the extra bristle phenotype of pyd^J14/pyd^C5 flies. Overexpression of Pyd 6^- in a second independent hs-pyd6^- transgenic line also fails to rescue the lethal phenotype of pyd^C5, but does suppress the extra bristle phenotype of pyd^J14/pyd^C5 flies. A similar suppression of the extra bristle phenotype is observed with overexpression of the pyd6⁺ cDNA, suggesting that both isoforms can function in SOP patterning. Overexpression of both isoforms simultaneously produces a more complete suppression of the extra bristle phenotype than either isoform alone, suggesting that both isoforms are involved in patterning of SOPs (Wei, 2001).

Effects of Mutation or Deletion

In Drosophila sensory organ development, the balance of activities between proneural genes and repressor genes defines a proneural cluster as a population of competent cells for neural development. The tamou gene (Tamou means 'hairy' in Japanese), now termed polychaetoid, encodes a cell-cell junction-associated protein, which is homologous to mammalian ZO-1, a member of the membrane-associated guanylate kinase homolog family. The polychaetoid mutation reduces the transcription of a repressor gene, extramacrochaetae, and causes enlargement of a proneural cluster where supernumerary precursor cells emerge, resulting in extra mechanosensory organs in the fly. Homozygotes of tam1, a mutation caused by a P-element insertion, are fully viable and fertile but ectopic macrochaetae are conspicuous on the dorsal side of the head and thorax of adults. The P-element insertion is 85 bases upstream of the 5'-terminal of the cDNA. The ectopic macrochaetae are not uniformly distributed on the notum, since almost all of them emerge near the positions of the dorsocentral (DC), postalar (PA) and/or scutellar (SCu) bristles, and rarely form near the postions of the supraalar or presutural bristles. The microchaete distribution pattern is slightly affected by the ectopic microchaetae formed between the rows of normal microchaete; however, the spacing of the microchaetae within each row seem normal. These phenotypes resemble those of some hypomorphic alleles of extramacrochaetae. Daughter cells of single sensory organ precursor (SOP) cells are known to be closely associated with one another during sensory organ development. In the tam1 mutant, epithelial cells are always observed between the bristles of the notum. Therefore, the ectopic bristle (shaft and socket) do not seem to be generated by the transformation of daughter cells, which normally give rise to a sheath cell and a neuron, leading to the prediction that the additional bristle in the tam1 mutant appear through the formation of additional SOPs (Takahisa, 1996).

In the most severe pyd genotypes, nearly all macrochaetae positions on the head and notum are affected. However, individual macrochaete positions display differences in sensitivity to reduction of pyd function: in general, as the level of pyd function decreases, more positions are affected and the number of extra bristles at the most sensitive positions increases. However, it is not possible to define an allelic series that is consistent for all macrochaete positions. A slight increase in macrochaete density is noted in pyd mutants. A reduction in pyd function results in the formation of additional SOPs in proneural clusters. In pyd mutant discs, the proneural cluster pattern of Achaete expression appears unchanged from the wild-type pattern: ectopic expression of Achaete is not observed. However, the subsequent refinement of Achaete expression is altered as additional cells express the high levels of Achaete characteristic of SOPs. In many pyd mutants, SOPs within a single cluster appear to be at different stages, as reflected in the normal transition from Achaete to Asense expression (Chen, 1996).

polychaetoid is required for cell fate specification in the eye. In pyd mutants a slight roughness of the eye is detected. This roughness is due to the presence of mispositioned and duplicated mechanosensory bristles and occasional enlarged, irregularly shaped facets. In addition, the rows of ommatidia are misaligned. In the midpupal stage eyes of pyd mutants, a small fraction of ommatidia are observed to have extra cone cells and/or primary pigment cells. Some ommatidia have too few cone cells. Ommatidia with extra cone cells also have extra photoreceptors. Reduction of Delta or Notch function in pyd mutants strongly enhances both the pyd extra bristle and rough eye phenotypes (Chen, 1996).

Polychaetoid is required for cell specification and rearrangement during Drosophila tracheal morphogenesis

The development of the complex network of epithelial tubes that ultimately forms the Drosophila tracheal system relies on cell migration, cell shape changes, cell rearrangements, cell differentiation, and branch fusion. Most of these events are controlled by a combination of distinct transcription factors and cell-cell signaling molecules, but few proteins that do not fall within these two functional classes have been associated with tracheal development. This study shows that the MAGUK protein Polychaetoid (Pyd/ZO-1), the Drosophila homolog of the junctional protein ZO-1, plays a dual role in the formation of tracheal tubes. pyd/ZO-1 mutant embryos display branch fusion defects due to the lack of reliable determination of the fusion cell fate. In addition, pyd/ZO-1 mutant embryos show impaired cell intercalation in thin tracheal branches. Pyd/ZO-1 localizes to the adherens junctions (AJs) in tracheal cells and might thus play a direct role in the regulation of the dynamic state of the AJ during epithelial remodeling. This study suggests that MAGUK proteins might play important roles during AJ remodeling in epithelial morphogenesis (Jung, 2006).

Cell fate determination in the Drosophila tracheal system is regulated by the Trachealess (Trh) transcription factor. In order to identify novel Trh target genes, a comparison of the transcriptional profiles of wild-type and loss-of-function trh mutant Drosophila stage 11 embryos was compared using the Affymetrix GeneChip technology. It was found the expression of the polychaetoid (pyd) gene is downregulated in a trh mutant background. pyd/ZO-1 is expressed in the tracheal placodes of stage 11 embryos. Expression was also observed in the foregut and hindgut and in the epidermis. In trh mutant embryos, pyd/ZO-1 transcription is still observed in the epidermis, the foregut, and the hindgut but was absent from the tracheal placodes. pyd/ZO-1 encodes the Drosophila homolog of the vertebrate cell-cell junction-associated protein zonula occludens 1 (ZO-1) and is a member of the MAGUK family of proteins (Jung, 2006).

MAGUK proteins are known to be incorporated in macromolecular protein complexes located at the tight junctions (TJs) in vertebrates. In Drosophila, Pyd/ZO-1 localizes to the adherens junctions (AJs) of the embryonic epidermis and the larval imaginal disc epithelium. An N-terminal eGFP-tagged full-length Pyd/ZO-1 protein was expressed in tracheal cells under the control of the btl-Gal4 driver and a GFP signal was observed at the level of intercellular AJs of the dorsal trunk (DT) in a mesh-like pattern similar to the D-α-catenin-GFP and Shotgun/E-cadherin-GFP (Shg/E-Cad-GFP) fusion constructs. GFP fluorescence was also seen in single lines corresponding to the autocellular AJs of the dorsal branches (DBs), the ganglionic branches (GBs), and the lateral trunk (LT). Double-labeling experiments showed a colocalization of the GFP-Pyd fusion construct and Shg/E-Cad at the AJs in the tracheal system. These results demonstrate that Pyd/ZO-1 is enriched with Shg/E-Cad and D-α-catenin-GFP at the AJs of tracheal cells (Jung, 2006).

Since the DB fusion-defect phenotype is not fully penetrant, occurring phenotypes were grouped into three categories: only one metamere affected (weak phenotype), two to four metameres affected (intermediate phenotype), and five or more metameres affected (severe phenotype). The results suggest that pyd/ZO-1 is required for proper fusion of the DBs and, to a lesser extent, the LT, as well as for proper outgrowth of the GBs. These phenotypes are due to specific lesions in the pyd/ZO-1 locus, as shown by the rescue experiments (Jung, 2006).

Terminal- and fusion-cell fate determination was examined by analyzing both blistered/Drosophila serum reponse factor (bs/Dsrf) and escargot (esg) expression patterns in pyd/ZO-1 loss-of-function mutant embryos. It was found that, instead of a single Bs/Dsrf-expressing cell at the tip of DBs, some DBs were characterized by the presence of an ectopic terminal cell in pyd/ZO-1 mutants. This situation is similar to the previously reported ectopic expression of acheate and asense in Drosophila wing imaginal discs of pyd/ZO-1 mutants, with consequent formation of extra macrochaetes on the adult notum. Using an esg-lacZ line, it was observed that in wild-type embryos or pyd^C5 heterozygous embryos, one single lacZ-positive fusion cell is found at the tip of each DB, whereas in pyd^C5 homozygous individuals, anti-β-galactosidase staining was absent in some DBs that had failed to undergo branch fusion. It was confirmed that branches that had not fused showed an excess of terminal cells and a loss of fusion cells by using the esg-lacZ; pyd^C5 strain to perform a 2A12/Dsrf/β-galactosidase triple immunostaining. These results suggest that pyd/ZO-1 is involved in fusion- versus terminal-cell specification via the regulation of bs/Dsrf or esg gene expression (Jung, 2006).

Interestingly, DBs with a wild-type Dsrf and Esg pattern (one terminal cell and one fusion cell) were identified, that did not undergo branch fusion. Therefore, it appears that the cell fate shift observed in pyd/ZO-1 mutants does not alone explain all fusion defects, and xa mechanical role of Pyd/ZO-1 in the branch fusion process itself cannot be excluded (Jung, 2006).

To determine whether pyd/ZO-1 function is required in the terminal or in the fusion cell, clonal analysis was performed in mosaic third-instar larvae using the MARCM system. pyd/ZO-1 mutant clones affecting the terminal cells did not affect branch fusion to a significant extent. However, most pyd/ZO-1 mutant clones including the fusion cells were associated with branch fusion defects, whereas only a few DBs displaying pyd/ZO-1 mutant fusion cells showed a wild-type branch fusion pattern. In some cases, it was observed that pyd/ZO-1 homozygous mutant cells in the position of the fusion cell displayed ectopic terminal branches, an observation that is reminiscent of the esg loss-of-function phenotype. It was therefore concluded that pyd/ZO-1 acts in the fusion cell to specify fusion- versus terminal-cell fate (Jung, 2006).

It was observed that overexpression of pyd/ZO-1 in tracheal cells of wild-type embryos mimics the pyd/ZO-1 DB fusion-defect phenotype. Taken together, these results suggest a model in which Pyd/ZO-1 regulates the subcellular localization and/or activation of a factor of unknown nature involved in the regulation of gene expression by either inducing the fusion-cell fate or repressing the terminal-cell fate in the fusion cell (Jung, 2006).

Several MAGUK proteins are known to be used as scaffold proteins organizing signaling pathways . pyd/ZO-1 itself regulates the expression of the acheate-scute gene complex. Further insights into the molecular aspects of this regulation will provide a clearer idea about how Pyd/ZO-1 fulfills its function (Jung, 2006).

Sincc these results indicated that Pyd/ZO-1 localizes to the AJs of the tracheal system, the dynamics of tracheal cell rearrangements were analyzed by examining the D-α-catenin-GFP pattern in pyd/ZO-1 mutant embryos using confocal live imaging techniques. In stage 16 wild-type embryos, the cell rearrangement process is completed in unicellular branches. Cells are in an end-to-end configuration, with long lines of autocellular AJs and very tiny rings of intercellular AJs. In contrast to these control embryos, large loops of intercellular AJs remained in fine branches of pyd homozygous embryos, indicating that cell intercalation was not completed. These cell intercalation defects were not fully penetrant. In the case of the strongest allele with regard to this intercalation phenotype, 26% of the DBs were affected; this phenotype was never observed in wild-type embryos (Jung, 2006).

Strikingly, in most cases, DBs with a cell intercalation phenotype were still able to stretch and eventually reached the dorsal midline. Some were even able to undergo branch fusion. These results suggest that branch fusion and branch stretching are not required for DB cell intercalation and vice versa. Similar observations were made in the case of the LT, where loops of D-α-catenin-GFP were still present between LT cells although adjacent metameres had undergone fusion (Jung, 2006).

It was observed that pyd/ZO-1 mutant embryos showed GB outgrowth defects. Defective cell intercalation was also found in GBs, and affected branches were shorter than neighboring GBs. Therefore, it is proposed that, in contrast to DBs, proper cell intercalation is necessary for GBs to adopt an elongated tube shape (Jung, 2006).

Expression of the GFP-pyd construct in the tracheal system of BG02748 homozygous embryos allowed a full rescue of the intercalation phenotype, even though DB fusion defects were not fully rescued. A live confocal time-lapse analysis was performed and it was observed that, in contrast to stage 16 heterozygous pyd^C5 embryos, in which DB cells were intercalated and remained so until the end of the analysis, homozygous pyd^C5 embryos of the same age showed cell intercalation defects where loops of D-α-catenin-GFP were interspersed with autocellular AJs. It is concluded that the zipping process seems to be stopped or frozen, leaving pairs of cells in a partially intercalated state. It was not observe that autocellular AJs converted back into intercellular AJs, which could also have been a possible explanation for the phenotype. It is very likely that Pyd/ZO-1 is part of the adhesion E-cadherin/α-/β-catenin protein complex that governs cell-cell adhesion (Jung, 2006).

Altogether, these results suggest a role for pyd/ZO-1 in facilitating the cell rearrangement process that underlies the formation of fine, elongated tubes with autocellular AJs in the tracheal system. This phenotype appears to be functionally independent from the branch-fusion-defect phenotype (Jung, 2006).

This study has shown that Pyd/ZO-1 plays a dual role during the morphogenesis of the Drosophila tracheal system and it is proposed that the transcriptional and mechanistic roles of pyd/ZO-1 are independent. This suggests that Pyd/ZO-1 uses distinct partners to achieve its two functions in the tracheal system. This is the first report of an in vivo analysis of pyd/ZO-1 in a cell biological process, and Pyd/ZO-1 is the first junction-associated protein described to have an effect on cell rearrangements during tracheal branching morphogenesis (Jung, 2006).

Aaku-Saraste, E., Hellwig, A., and Huttner, W. B. (1996). Loss of occludin and functional tight junctions, but not ZO-1, during neural tube closure--remodeling of the neuroepithelium prior to neurogenesis. Dev. Biol. 180: 664-679. PubMed citation: 8954735

Araújo, S. J., Cela, C. and Llimargas, M. (2007). Tramtrack regulates different morphogenetic events during Drosophila tracheal development. Development 134(20): 3665-76. PubMed citation: 17881489

Balda, M. S. and Matter, K. (2000). The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression. EMBO J. 19: 2024-2033. PubMed citation: 10790369

Beatch, M., et al. (1996). The tight junction protein ZO-2 contains three PDZ (PSD-95/Discs-Large/ZO-1) domains and an alternatively spliced region. J. Biol. Chem. 271(42): 25723-6.

Buse, P., et al. (1995). Transforming growth factor-alpha abrogates glucocorticoid-stimulated tight junction formation and growth suppression in rat mammary epithelial tumor cells. J. Biol. Chem. 270: 6505-6514.

Chen, C. M., et al. (1996). polychaetoid is required to restrict segregation of sensory organ precursors from proneural clusters in Drosophila. Mech. Dev. 57(2): 215-27. PubMed citation: 8843398

Du, Y., et al. (1998). Identification of a novel cortactin SH3 domain-binding protein and its localization to growth cones of cultured neurons. Mol. Cell. Biol. 18(10): 5838-51.

Furuse, M., et al. (1994). Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. J. Cell Biol. 127(6 Pt 1): 1617-26. 95096174

Giepmans, B. N. and Moolenaar, W. H. (1998). The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein. Curr. Biol. 8(16): 931-4.

Gottardi, C. J., et al. (1996). The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts. Proc. Natl. Acad. Sci. 93(20): 10779-84.

Haskins, J., et al. (1998). ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J. Cell Biol. 141(1): 199-208.

He, H., et al. (1998). Role of phosphatidylinositol 4,5-bisphosphate in Ras/Rac-induced disruption of the cortactin-actomyosin II complex and malignant transformation. Mol. Cell. Biol. 18(7): 3829-37. 98298227

Huang, C., et al. (1997). Down-regulation of the filamentous actin cross-linking activity of cortactin by Src-mediated tyrosine phosphorylation. J. Biol. Chem. 272(21): 13911-5. 97298104

Huang, C., et al. (1998). The role of tyrosine phosphorylation of cortactin in the locomotion of endothelial cells. J. Biol. Chem. 273(40): 25770-6.

Imamura, Y., et al. (1999). Functional domains of alpha-Catenin required for the strong state of Cadherin-based cell adhesion. J. Cell Biol. 144(6): 1311-1322

Itoh, M., et al. (1993). The 220-kD protein colocalizing with cadherins in non-epithelial cells is identical to ZO-1, a tight junction-associated protein in epithelial cells: cDNA cloning and immunoelectron microscopy. J. Cell Biol. 121(3): 491-502.

Itoh, M., et al. (1997). Involvement of ZO-1 in cadherin-based cell adhesion through its direct binding to alpha catenin and actin filaments. J. Cell Biol. 138(1): 181-192.

Jesaitis, L. A. and Goodenough, D. A. (1994). Molecular characterization and tissue distribution of ZO-2, a tight junction protein homologous to ZO-1 and the Drosophila discs-large tumor suppressor protein. J. Cell Biol. 124: 949-61

Jung, A. C., et al. (2006). Polychaetoid/ZO-1 is required for cell specification and rearrangement during Drosophila tracheal morphogenesis. Curr. Biol. 16: 1224-1231. 16782014

Katsube, T., et al. (1998). Cortactin associates with the cell-cell junction protein ZO-1 in both Drosophila and mouse. J. Biol. Chem. 273(45): 29672-7.

Kim, L. and Wong, T. W. (1998). Growth factor-dependent phosphorylation of the actin-binding protein cortactin is mediated by the cytoplasmic tyrosine kinase FER. J. Biol. Chem. 273(36):23542-8.

Kinnunen, T., et al. (1998). Cortactin-Src kinase signaling pathway is involved in N-syndecan-dependent neurite outgrowth. J. Biol. Chem. 273(17):10702-8.

Kuriyama, M., et al. (1996). Identification of AF-6 and canoe as putative targets for Ras. J. Biol. Chem. 271(2): 607-610. 96132780

McGee, A. W. and Bredt, D. S. (1999). Identification of an intramolecular interaction between the SH3 and Guanylate Kinase Domains of PSD-95. J. Biol. Chem. 274: 17431-17436.

Mitic, L. L., et al. (1999). Connexin-Occludin chimeras containing the ZO-binding domain of Occludin localize at MDCK tight junctions and NRK cell contacts. J. Cell Biol. 146: 683-693.

Miyamoto, H., et al. (1995). canoe encodes a novel protein containing a GLGF/DHR motif and functions with Notch and scabrous in common developmental pathways in Drosophila. Genes Dev 9: 612-625.

Paria, B. C., et al. (1999). Zonula occludens-1 and E-cadherin are coordinately expressed in the mouse uterus with the initiation of implantation and decidualization. Dev. Biol. 208(2): 488-501.

Peng, H. B., Xie, H. and Dai, Z. (1997). Association of cortactin with developing neuromuscular specializations. J. Neurocytol. 26(10): 637-50.

Roh, M. H., et al. (2002). The carboxyl terminus of Zona occludens-3 binds and recruits a mammalian homologue of Discs lost to tight junctions. J. Biol. Chem. 277: 27501-27509. 12021270

Rosato, R., et al. (1998). Involvement of the tyrosine kinase fer in cell adhesion. Mol. Cell. Biol. 18(10): 5762-70.

Sheth, B., et al. (1997). Tight junction assembly during mouse blastocyst formation is regulated by late expression of ZO-1 alpha+ isoform. Development 124(10): 2027-37.

Stuart, R. O. and Nigam, S. K. (1995). Regulated assembly of tight junctions by protein kinase C. Proc. Natl. Acad. Sci. 92: 6072-6076.

Takahashi, K., et al. (1998). Direct binding between two PDZ domain proteins Canoe and ZO-1 and their roles in regulation of the Jun N-terminal kinase pathway in Drosophila morphogenesis. Mech. Dev. 78(1-2): 97-111.

Takahisa, M., et al. (1996). The Drosophila tamou gene, a component of the activating pathway of extramacrochaetae expression, encodes a protein homologous to mammalian cell-cell junction-associated protein ZO-1. Genes Dev. 10(14): 1783-95.

Weed, S. A., Du, Y. and Parsons, J. T. (1998). Translocation of cortactin to the cell periphery is mediated by the small GTPase Rac1. J. Cell Sci. 111 ( Pt 16): 2433-43.

Wei, X. and Ellis, H. M. (2001). Localization of the Drosophila MAGUK protein Polychaetoid is controlled by alternative splicing. Mech. Dev. 100: 217-231. 11165479

Willott, E., et al. (1993). The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. Proc. Natl. Acad. Sci. 90: 7834-8

Wittchen, E. S., Haskins, J. and Stevenson, B. R. (2000). Exogenous expression of the amino-terminal half of the tight junction protein ZO-3 perturbs junctional complex assembly. J. Cell Biol. 151(4): 825-836. 11076967

Wu, H. and Parsons, J. T. (1993). Cortactin, an 80/85-kilodalton pp60src substrate, is a filamentous actin-binding protein enriched in the cell cortex. J. Cell Biol. 120(6): 1417-26.

Yamamoto, T., et al. (1997). The Ras target AF-6 interacts with ZO-1 and serves as a peripheral component of tight junctions in epithelial cells. J. Cell Biol. 139: 785-795.

Yokoyama, S., et al. (2001). alpha-Catenin-independent recruitment of ZO-1 to nectin-based cell-cell adhesion sites through afadin. Mol. Biol. Cell 12: 1595-1609. 11408571

date revised: 20 April 2008

Home page: The Interactive Fly © 1997 Thomas B. Brody, Ph.D

The Interactive Fly resides on the
Society for Developmental Biology's Web server.