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Abelson kinase regulates epithelial morphogenesis in Drosophila.

Grevengoed EE, Loureiro JJ, Jesse TL, Peifer M - J. Cell Biol. (2001)

Bottom Line: The defects of abl mutants are strongly enhanced by heterozygosity for shotgun, which encodes DE-cadherin.Finally, loss of Abl reduces Arm and alpha-catenin accumulation in adherens junctions, while having little or no effect on other components of the cytoskeleton or cell polarity machinery.We discuss possible models for Abl function during epithelial morphogenesis in light of these data.

View Article: PubMed Central - PubMed

Affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.

ABSTRACT
Activation of the nonreceptor tyrosine kinase Abelson (Abl) contributes to the development of leukemia, but the complex roles of Abl in normal development are not fully understood. Drosophila Abl links neural axon guidance receptors to the cytoskeleton. Here we report a novel role for Drosophila Abl in epithelial cells, where it is critical for morphogenesis. Embryos completely lacking both maternal and zygotic Abl die with defects in several morphogenetic processes requiring cell shape changes and cell migration. We describe the cellular defects that underlie these problems, focusing on dorsal closure as an example. Further, we show that the Abl target Enabled (Ena), a modulator of actin dynamics, is involved with Abl in morphogenesis. We find that Ena localizes to adherens junctions of most epithelial cells, and that it genetically interacts with the adherens junction protein Armadillo (Arm) during morphogenesis. The defects of abl mutants are strongly enhanced by heterozygosity for shotgun, which encodes DE-cadherin. Finally, loss of Abl reduces Arm and alpha-catenin accumulation in adherens junctions, while having little or no effect on other components of the cytoskeleton or cell polarity machinery. We discuss possible models for Abl function during epithelial morphogenesis in light of these data.

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Ena and Arm colocalize at adherens junctions throughout development. All images (except I) are anterior to the right. Ena is green and Arm is red in merged images. (A) Stage 3 egg chamber. Ena and Arm are enriched in apical adherens junctions of follicle cells. (B and C) Stage 10 egg chamber. Levels of Ena and Arm drop, but both remain at adherens junctions. Anterior (border cells) and posterior polar follicle cells are enriched in both Ena and Arm (B, arrows). Ena and Arm also colocalize to nurse cell membranes (B, arrowhead). (D–G) During embryogenesis Ena and Arm colocalize to adherens junctions of epithelial tissues. (D) Cross-section, stage 9 embryo. Ectodermal adherens junctions (arrow). (E) Adherens junctions of polarized cells of the invaginating hindgut (arrow). (F) Apical view, stage 9 embryo. Ena is enriched at vertices of cell–cell contact (arrow), whereas Arm is more uniform. (G) During dorsal closure Ena is enriched at adherens junctions of leading edge cells, but it is also found in the cytoplasm of cells at the segment boundary (arrowheads). (H) Ena and Arm both localize to axons. (I–K) Imaginal discs. (I) Apical surfaces of two epithelial sheets opposed to one another in the wing imaginal disc (arrow). Ena and Arm colocalize to apical adherens junctions, and are also found at the apical surface. (J and K) In eye imaginal discs cell differentiation occurs after the morphogenetic furrow passes. In undifferentiated cells, Ena and Arm colocalize to cell boundaries (J, arrowhead). As groups of cells begin differentiating as photoreceptors (J, arrow), Ena localizes uniformly to all cells of the precluster. Arm, in contrast, accumulates at high levels in a subset of these cells. Later, Ena and Arm colocalize in photoreceptor rhabdomeres (K, arrow). Bars: (A–J) 10 μm; (K) 50 μm.
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fig6: Ena and Arm colocalize at adherens junctions throughout development. All images (except I) are anterior to the right. Ena is green and Arm is red in merged images. (A) Stage 3 egg chamber. Ena and Arm are enriched in apical adherens junctions of follicle cells. (B and C) Stage 10 egg chamber. Levels of Ena and Arm drop, but both remain at adherens junctions. Anterior (border cells) and posterior polar follicle cells are enriched in both Ena and Arm (B, arrows). Ena and Arm also colocalize to nurse cell membranes (B, arrowhead). (D–G) During embryogenesis Ena and Arm colocalize to adherens junctions of epithelial tissues. (D) Cross-section, stage 9 embryo. Ectodermal adherens junctions (arrow). (E) Adherens junctions of polarized cells of the invaginating hindgut (arrow). (F) Apical view, stage 9 embryo. Ena is enriched at vertices of cell–cell contact (arrow), whereas Arm is more uniform. (G) During dorsal closure Ena is enriched at adherens junctions of leading edge cells, but it is also found in the cytoplasm of cells at the segment boundary (arrowheads). (H) Ena and Arm both localize to axons. (I–K) Imaginal discs. (I) Apical surfaces of two epithelial sheets opposed to one another in the wing imaginal disc (arrow). Ena and Arm colocalize to apical adherens junctions, and are also found at the apical surface. (J and K) In eye imaginal discs cell differentiation occurs after the morphogenetic furrow passes. In undifferentiated cells, Ena and Arm colocalize to cell boundaries (J, arrowhead). As groups of cells begin differentiating as photoreceptors (J, arrow), Ena localizes uniformly to all cells of the precluster. Arm, in contrast, accumulates at high levels in a subset of these cells. Later, Ena and Arm colocalize in photoreceptor rhabdomeres (K, arrow). Bars: (A–J) 10 μm; (K) 50 μm.

Mentions: These data suggest that Ena misregulation contributes to the defects in morphogenesis we observed in ablMZ mutants. We thus examined Ena localization in epithelial tissues, as this might reveal, at least in part, where Abl is acting. We used two different anti-Ena antibodies (Gertler et al., 1995; Bashaw et al., 2000) with similar results. We found that Ena colocalizes with Arm at adherens junctions throughout most stages of development. During early oogenesis, Ena and Arm are strongly enriched at adherens junctions of follicle cells surrounding the germline (Fig. 6 A; Baum and Perrimon, 2001) and remain enriched at junctions, though at lower levels as oogenesis proceeds (Figs. 6, B and C). During embryogenesis, Ena begins to accumulate in adherens junctions at the onset of gastrulation (unpublished data) and colocalizes with Arm at adherens junctions in germband-extended embryos (Fig. 6 D, arrow) and in fully polarized cells, such as the invaginating hindgut (Fig. 6 E, arrow). Arm localizes uniformly around cells (Fig. 6 F), whereas Ena, though present all around the plasma membrane, is enriched at vertices of cell–cell contact (Fig. 6 F, arrow). Ena is strongly enriched in adherens junctions of leading edge cells during dorsal closure (Figs. 4 C and 6 G), and also localizes to the cytoplasm in a stripe of epidermal cells at the segmental boundary (Fig. 6 G, arrowheads). Ena and Arm also localize to CNS axons (Gertler et al., 1990; Fig. 6 H). During larval development, Ena and Arm are strongly enriched at adherens junctions of the highly polarized imaginal disc epithelia, precursors of the adult epidermis (Figs. 6 I, arrow), as well as in the specialized junctions of the photoreceptor rhabdomeres (Fig. 6, J and K). Thus, Arm and Ena colocalize in adherens junctions in most epithelial cells.


Abelson kinase regulates epithelial morphogenesis in Drosophila.

Grevengoed EE, Loureiro JJ, Jesse TL, Peifer M - J. Cell Biol. (2001)

Ena and Arm colocalize at adherens junctions throughout development. All images (except I) are anterior to the right. Ena is green and Arm is red in merged images. (A) Stage 3 egg chamber. Ena and Arm are enriched in apical adherens junctions of follicle cells. (B and C) Stage 10 egg chamber. Levels of Ena and Arm drop, but both remain at adherens junctions. Anterior (border cells) and posterior polar follicle cells are enriched in both Ena and Arm (B, arrows). Ena and Arm also colocalize to nurse cell membranes (B, arrowhead). (D–G) During embryogenesis Ena and Arm colocalize to adherens junctions of epithelial tissues. (D) Cross-section, stage 9 embryo. Ectodermal adherens junctions (arrow). (E) Adherens junctions of polarized cells of the invaginating hindgut (arrow). (F) Apical view, stage 9 embryo. Ena is enriched at vertices of cell–cell contact (arrow), whereas Arm is more uniform. (G) During dorsal closure Ena is enriched at adherens junctions of leading edge cells, but it is also found in the cytoplasm of cells at the segment boundary (arrowheads). (H) Ena and Arm both localize to axons. (I–K) Imaginal discs. (I) Apical surfaces of two epithelial sheets opposed to one another in the wing imaginal disc (arrow). Ena and Arm colocalize to apical adherens junctions, and are also found at the apical surface. (J and K) In eye imaginal discs cell differentiation occurs after the morphogenetic furrow passes. In undifferentiated cells, Ena and Arm colocalize to cell boundaries (J, arrowhead). As groups of cells begin differentiating as photoreceptors (J, arrow), Ena localizes uniformly to all cells of the precluster. Arm, in contrast, accumulates at high levels in a subset of these cells. Later, Ena and Arm colocalize in photoreceptor rhabdomeres (K, arrow). Bars: (A–J) 10 μm; (K) 50 μm.
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fig6: Ena and Arm colocalize at adherens junctions throughout development. All images (except I) are anterior to the right. Ena is green and Arm is red in merged images. (A) Stage 3 egg chamber. Ena and Arm are enriched in apical adherens junctions of follicle cells. (B and C) Stage 10 egg chamber. Levels of Ena and Arm drop, but both remain at adherens junctions. Anterior (border cells) and posterior polar follicle cells are enriched in both Ena and Arm (B, arrows). Ena and Arm also colocalize to nurse cell membranes (B, arrowhead). (D–G) During embryogenesis Ena and Arm colocalize to adherens junctions of epithelial tissues. (D) Cross-section, stage 9 embryo. Ectodermal adherens junctions (arrow). (E) Adherens junctions of polarized cells of the invaginating hindgut (arrow). (F) Apical view, stage 9 embryo. Ena is enriched at vertices of cell–cell contact (arrow), whereas Arm is more uniform. (G) During dorsal closure Ena is enriched at adherens junctions of leading edge cells, but it is also found in the cytoplasm of cells at the segment boundary (arrowheads). (H) Ena and Arm both localize to axons. (I–K) Imaginal discs. (I) Apical surfaces of two epithelial sheets opposed to one another in the wing imaginal disc (arrow). Ena and Arm colocalize to apical adherens junctions, and are also found at the apical surface. (J and K) In eye imaginal discs cell differentiation occurs after the morphogenetic furrow passes. In undifferentiated cells, Ena and Arm colocalize to cell boundaries (J, arrowhead). As groups of cells begin differentiating as photoreceptors (J, arrow), Ena localizes uniformly to all cells of the precluster. Arm, in contrast, accumulates at high levels in a subset of these cells. Later, Ena and Arm colocalize in photoreceptor rhabdomeres (K, arrow). Bars: (A–J) 10 μm; (K) 50 μm.
Mentions: These data suggest that Ena misregulation contributes to the defects in morphogenesis we observed in ablMZ mutants. We thus examined Ena localization in epithelial tissues, as this might reveal, at least in part, where Abl is acting. We used two different anti-Ena antibodies (Gertler et al., 1995; Bashaw et al., 2000) with similar results. We found that Ena colocalizes with Arm at adherens junctions throughout most stages of development. During early oogenesis, Ena and Arm are strongly enriched at adherens junctions of follicle cells surrounding the germline (Fig. 6 A; Baum and Perrimon, 2001) and remain enriched at junctions, though at lower levels as oogenesis proceeds (Figs. 6, B and C). During embryogenesis, Ena begins to accumulate in adherens junctions at the onset of gastrulation (unpublished data) and colocalizes with Arm at adherens junctions in germband-extended embryos (Fig. 6 D, arrow) and in fully polarized cells, such as the invaginating hindgut (Fig. 6 E, arrow). Arm localizes uniformly around cells (Fig. 6 F), whereas Ena, though present all around the plasma membrane, is enriched at vertices of cell–cell contact (Fig. 6 F, arrow). Ena is strongly enriched in adherens junctions of leading edge cells during dorsal closure (Figs. 4 C and 6 G), and also localizes to the cytoplasm in a stripe of epidermal cells at the segmental boundary (Fig. 6 G, arrowheads). Ena and Arm also localize to CNS axons (Gertler et al., 1990; Fig. 6 H). During larval development, Ena and Arm are strongly enriched at adherens junctions of the highly polarized imaginal disc epithelia, precursors of the adult epidermis (Figs. 6 I, arrow), as well as in the specialized junctions of the photoreceptor rhabdomeres (Fig. 6, J and K). Thus, Arm and Ena colocalize in adherens junctions in most epithelial cells.

Bottom Line: The defects of abl mutants are strongly enhanced by heterozygosity for shotgun, which encodes DE-cadherin.Finally, loss of Abl reduces Arm and alpha-catenin accumulation in adherens junctions, while having little or no effect on other components of the cytoskeleton or cell polarity machinery.We discuss possible models for Abl function during epithelial morphogenesis in light of these data.

View Article: PubMed Central - PubMed

Affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.

ABSTRACT
Activation of the nonreceptor tyrosine kinase Abelson (Abl) contributes to the development of leukemia, but the complex roles of Abl in normal development are not fully understood. Drosophila Abl links neural axon guidance receptors to the cytoskeleton. Here we report a novel role for Drosophila Abl in epithelial cells, where it is critical for morphogenesis. Embryos completely lacking both maternal and zygotic Abl die with defects in several morphogenetic processes requiring cell shape changes and cell migration. We describe the cellular defects that underlie these problems, focusing on dorsal closure as an example. Further, we show that the Abl target Enabled (Ena), a modulator of actin dynamics, is involved with Abl in morphogenesis. We find that Ena localizes to adherens junctions of most epithelial cells, and that it genetically interacts with the adherens junction protein Armadillo (Arm) during morphogenesis. The defects of abl mutants are strongly enhanced by heterozygosity for shotgun, which encodes DE-cadherin. Finally, loss of Abl reduces Arm and alpha-catenin accumulation in adherens junctions, while having little or no effect on other components of the cytoskeleton or cell polarity machinery. We discuss possible models for Abl function during epithelial morphogenesis in light of these data.

Show MeSH
Related in: MedlinePlus