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Regulatory mechanisms required for DE-cadherin function in cell migration and other types of adhesion.

Pacquelet A, Rørth P - J. Cell Biol. (2005)

Bottom Line: We have investigated the requirements for Drosophila melanogaster epithelial (DE) cadherin regulation in vivo.We found that (1) although linking DE-cadherin to alpha-catenin is essential, regulation of the link is not required in any of these types of adhesion; (2) beta-catenin is required only to link DE-cadherin to alpha-catenin; and (3) the cytoplasmic domain of DE-cadherin has an additional specific function for the invasive migration of border cells, which is conserved to other cadherins.The nature of this additional function is discussed.

View Article: PubMed Central - PubMed

Affiliation: European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.

ABSTRACT
Cadherin-mediated adhesion can be regulated at many levels, as demonstrated by detailed analysis in cell lines. We have investigated the requirements for Drosophila melanogaster epithelial (DE) cadherin regulation in vivo. Investigating D. melanogaster oogenesis as a model system allowed the dissection of DE-cadherin function in several types of adhesion: cell sorting, cell positioning, epithelial integrity, and the cadherin-dependent process of border cell migration. We generated multiple fusions between DE-cadherin and alpha-catenin as well as point-mutated beta-catenin and analyzed their ability to support these types of adhesion. We found that (1) although linking DE-cadherin to alpha-catenin is essential, regulation of the link is not required in any of these types of adhesion; (2) beta-catenin is required only to link DE-cadherin to alpha-catenin; and (3) the cytoplasmic domain of DE-cadherin has an additional specific function for the invasive migration of border cells, which is conserved to other cadherins. The nature of this additional function is discussed.

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DE-cadherin function during oogenesis. (A) Schematic representation of border cell migration. (B) Wild-type stage 10 egg chamber; border cells (arrow) have reached the oocyte. (C) Border cells (arrow) do not migrate when border or nurse cells are mutant for shg (DE-cadherin). (D) The oocyte (asterisks) is located in the posterior of wild-type egg chambers. (E) Oocyte mislocalization is often observed when follicle or nurse cells are shg mutant. (F and G) Follicle cell sorting; stage 9 egg chambers. Compared with control clones (F), shg mutant clones sort away from wild-type cells to form a smooth interface (G). (H and I) Follicular epithelium integrity; stage 10 egg chambers. shg mutant clones lose epithelial integrity (I, compare cell shape with that of the wild-type clone in H). (B–I) Phalloidin (red) stains F-actin. (F–I) Mutant clones are indicated by an absence of GFP (green). Bars (B and C), 80 μm; (D and E) 50 μm; (F–I) 20 μm.
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fig1: DE-cadherin function during oogenesis. (A) Schematic representation of border cell migration. (B) Wild-type stage 10 egg chamber; border cells (arrow) have reached the oocyte. (C) Border cells (arrow) do not migrate when border or nurse cells are mutant for shg (DE-cadherin). (D) The oocyte (asterisks) is located in the posterior of wild-type egg chambers. (E) Oocyte mislocalization is often observed when follicle or nurse cells are shg mutant. (F and G) Follicle cell sorting; stage 9 egg chambers. Compared with control clones (F), shg mutant clones sort away from wild-type cells to form a smooth interface (G). (H and I) Follicular epithelium integrity; stage 10 egg chambers. shg mutant clones lose epithelial integrity (I, compare cell shape with that of the wild-type clone in H). (B–I) Phalloidin (red) stains F-actin. (F–I) Mutant clones are indicated by an absence of GFP (green). Bars (B and C), 80 μm; (D and E) 50 μm; (F–I) 20 μm.

Mentions: In this study, we use Drosophila melanogaster epithelial (DE) cadherin–mediated adhesion during D. melanogaster oogenesis as a model to study adhesion regulation in different types of adhesion in vivo. DE-cadherin is a classic cadherin that is encoded by the shotgun (shg) gene and is associated with junctional complexes in epithelia (Oda et al., 1994). During D. melanogaster oogenesis, DE-cadherin is also required for the invasive migration of border cells. Border cells are a group of about eight somatic follicle cells that delaminate from the follicular epithelium, invade the germ line cluster, and migrate to the oocyte (Fig. 1 A). Both border and nurse cells express DE-cadherin, and a lack of DE-cadherin in either cell type blocks migration (Fig. 1, B and C; Oda et al., 1997; Niewiadomska et al., 1999). This indicates that border cells adhere to the nurse cell substratum through homophilic DE-cadherin interaction and that this adhesion is essential for migration. For border cells to translocate, DE-cadherin–mediated adhesion may need to be effectively regulated to generate strong adhesion at the front as well as the release of adhesion in the back. To investigate DE-cadherin regulation in this context, we generated DE-cadherin mutant variants and analyzed their ability to replace the endogenous protein and support border cell migration. We also analyzed their ability to mediate other types of adhesion during D. melanogaster oogenesis. In D. melanogaster egg chambers, DE-cadherin is required to maintain epithelial integrity in follicle cells (Fig. 1, H and I; Tanentzapf et al., 2000). Moreover, it mediates differential cell affinities in the follicular epithelium as well as during oocyte positioning in egg chambers (Fig. 1, D–G; Godt and Tepass, 1998; González-Reyes and St. Johnston, 1998). Analyzing each of these processes allows us to distinguish general DE-cadherin function and regulation from migration-specific ones.


Regulatory mechanisms required for DE-cadherin function in cell migration and other types of adhesion.

Pacquelet A, Rørth P - J. Cell Biol. (2005)

DE-cadherin function during oogenesis. (A) Schematic representation of border cell migration. (B) Wild-type stage 10 egg chamber; border cells (arrow) have reached the oocyte. (C) Border cells (arrow) do not migrate when border or nurse cells are mutant for shg (DE-cadherin). (D) The oocyte (asterisks) is located in the posterior of wild-type egg chambers. (E) Oocyte mislocalization is often observed when follicle or nurse cells are shg mutant. (F and G) Follicle cell sorting; stage 9 egg chambers. Compared with control clones (F), shg mutant clones sort away from wild-type cells to form a smooth interface (G). (H and I) Follicular epithelium integrity; stage 10 egg chambers. shg mutant clones lose epithelial integrity (I, compare cell shape with that of the wild-type clone in H). (B–I) Phalloidin (red) stains F-actin. (F–I) Mutant clones are indicated by an absence of GFP (green). Bars (B and C), 80 μm; (D and E) 50 μm; (F–I) 20 μm.
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Related In: Results  -  Collection

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fig1: DE-cadherin function during oogenesis. (A) Schematic representation of border cell migration. (B) Wild-type stage 10 egg chamber; border cells (arrow) have reached the oocyte. (C) Border cells (arrow) do not migrate when border or nurse cells are mutant for shg (DE-cadherin). (D) The oocyte (asterisks) is located in the posterior of wild-type egg chambers. (E) Oocyte mislocalization is often observed when follicle or nurse cells are shg mutant. (F and G) Follicle cell sorting; stage 9 egg chambers. Compared with control clones (F), shg mutant clones sort away from wild-type cells to form a smooth interface (G). (H and I) Follicular epithelium integrity; stage 10 egg chambers. shg mutant clones lose epithelial integrity (I, compare cell shape with that of the wild-type clone in H). (B–I) Phalloidin (red) stains F-actin. (F–I) Mutant clones are indicated by an absence of GFP (green). Bars (B and C), 80 μm; (D and E) 50 μm; (F–I) 20 μm.
Mentions: In this study, we use Drosophila melanogaster epithelial (DE) cadherin–mediated adhesion during D. melanogaster oogenesis as a model to study adhesion regulation in different types of adhesion in vivo. DE-cadherin is a classic cadherin that is encoded by the shotgun (shg) gene and is associated with junctional complexes in epithelia (Oda et al., 1994). During D. melanogaster oogenesis, DE-cadherin is also required for the invasive migration of border cells. Border cells are a group of about eight somatic follicle cells that delaminate from the follicular epithelium, invade the germ line cluster, and migrate to the oocyte (Fig. 1 A). Both border and nurse cells express DE-cadherin, and a lack of DE-cadherin in either cell type blocks migration (Fig. 1, B and C; Oda et al., 1997; Niewiadomska et al., 1999). This indicates that border cells adhere to the nurse cell substratum through homophilic DE-cadherin interaction and that this adhesion is essential for migration. For border cells to translocate, DE-cadherin–mediated adhesion may need to be effectively regulated to generate strong adhesion at the front as well as the release of adhesion in the back. To investigate DE-cadherin regulation in this context, we generated DE-cadherin mutant variants and analyzed their ability to replace the endogenous protein and support border cell migration. We also analyzed their ability to mediate other types of adhesion during D. melanogaster oogenesis. In D. melanogaster egg chambers, DE-cadherin is required to maintain epithelial integrity in follicle cells (Fig. 1, H and I; Tanentzapf et al., 2000). Moreover, it mediates differential cell affinities in the follicular epithelium as well as during oocyte positioning in egg chambers (Fig. 1, D–G; Godt and Tepass, 1998; González-Reyes and St. Johnston, 1998). Analyzing each of these processes allows us to distinguish general DE-cadherin function and regulation from migration-specific ones.

Bottom Line: We have investigated the requirements for Drosophila melanogaster epithelial (DE) cadherin regulation in vivo.We found that (1) although linking DE-cadherin to alpha-catenin is essential, regulation of the link is not required in any of these types of adhesion; (2) beta-catenin is required only to link DE-cadherin to alpha-catenin; and (3) the cytoplasmic domain of DE-cadherin has an additional specific function for the invasive migration of border cells, which is conserved to other cadherins.The nature of this additional function is discussed.

View Article: PubMed Central - PubMed

Affiliation: European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.

ABSTRACT
Cadherin-mediated adhesion can be regulated at many levels, as demonstrated by detailed analysis in cell lines. We have investigated the requirements for Drosophila melanogaster epithelial (DE) cadherin regulation in vivo. Investigating D. melanogaster oogenesis as a model system allowed the dissection of DE-cadherin function in several types of adhesion: cell sorting, cell positioning, epithelial integrity, and the cadherin-dependent process of border cell migration. We generated multiple fusions between DE-cadherin and alpha-catenin as well as point-mutated beta-catenin and analyzed their ability to support these types of adhesion. We found that (1) although linking DE-cadherin to alpha-catenin is essential, regulation of the link is not required in any of these types of adhesion; (2) beta-catenin is required only to link DE-cadherin to alpha-catenin; and (3) the cytoplasmic domain of DE-cadherin has an additional specific function for the invasive migration of border cells, which is conserved to other cadherins. The nature of this additional function is discussed.

Show MeSH
Related in: MedlinePlus