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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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Complete loss of Abl alters Ena and actin localization during dorsal closure. Lateral view. Embryos double-labeled with anti-Ena (red) and phalloidin (green), labeling F-actin. (A) Stage 13 wild-type embryo with leading edge cells initiating elongation. Ena (left, red) is enriched at vertices of cell–cell contact. Actin (middle, green) outlines all cell membranes and is beginning to accumulate at the leading edge. Actin and Ena colocalize at cell junctions. (B) Stage 13 ablMZ mutant. Ena (left, red) and Actin (middle, green) enrichment is not uniform at the leading edge. Both are enriched in some cells (arrows) and depleted in others (brackets). (C) Stage 14 wild-type embryo. More lateral cells have undergone uniform elongation. Ena is uniformly enriched at adherens junctions of leading edge cells (left, red). Actin forms a tight cable along the leading edge (middle, green). Ena and actin colocalize at adherens junctions as actin expands along the entire leading edge. (D) Stage 14 ablMZ mutant. Nonuniform localization of Ena and Actin persists. Cells with excess Ena (left, arrow) often accumulate excess Actin (middle, arrow), whereas cells with diminished Ena levels (left, bracket) have diminished levels of Actin (middle, bracket) Bars, 10 μm.
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fig4: Complete loss of Abl alters Ena and actin localization during dorsal closure. Lateral view. Embryos double-labeled with anti-Ena (red) and phalloidin (green), labeling F-actin. (A) Stage 13 wild-type embryo with leading edge cells initiating elongation. Ena (left, red) is enriched at vertices of cell–cell contact. Actin (middle, green) outlines all cell membranes and is beginning to accumulate at the leading edge. Actin and Ena colocalize at cell junctions. (B) Stage 13 ablMZ mutant. Ena (left, red) and Actin (middle, green) enrichment is not uniform at the leading edge. Both are enriched in some cells (arrows) and depleted in others (brackets). (C) Stage 14 wild-type embryo. More lateral cells have undergone uniform elongation. Ena is uniformly enriched at adherens junctions of leading edge cells (left, red). Actin forms a tight cable along the leading edge (middle, green). Ena and actin colocalize at adherens junctions as actin expands along the entire leading edge. (D) Stage 14 ablMZ mutant. Nonuniform localization of Ena and Actin persists. Cells with excess Ena (left, arrow) often accumulate excess Actin (middle, arrow), whereas cells with diminished Ena levels (left, bracket) have diminished levels of Actin (middle, bracket) Bars, 10 μm.

Mentions: The defects in cell morphology during dorsal closure in ablMZ mutants led us to examine localization of actin and of the Abl target Ena, an actin regulator during this process. In the initial stages of dorsal closure, as cells along the leading edge begin to elongate, Ena surrounds the cell membrane but is enriched at vertices of cell–cell contact and at adherens junctions of leading edge cells (Fig. 4 A, left, red). Actin localizes around the entire cell and begins to accumulate at the leading edge at this stage (Fig. 4 A, middle, green; Young et al., 1993). As closure proceeds, Ena accumulates at uniformly high levels in adherens junctions of leading edge cells (Fig. 4 C, left, red), while actin forms a uniform and tightly localized band along the leading edge (Fig. 4 D middle, green).


Abelson kinase regulates epithelial morphogenesis in Drosophila.

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

Complete loss of Abl alters Ena and actin localization during dorsal closure. Lateral view. Embryos double-labeled with anti-Ena (red) and phalloidin (green), labeling F-actin. (A) Stage 13 wild-type embryo with leading edge cells initiating elongation. Ena (left, red) is enriched at vertices of cell–cell contact. Actin (middle, green) outlines all cell membranes and is beginning to accumulate at the leading edge. Actin and Ena colocalize at cell junctions. (B) Stage 13 ablMZ mutant. Ena (left, red) and Actin (middle, green) enrichment is not uniform at the leading edge. Both are enriched in some cells (arrows) and depleted in others (brackets). (C) Stage 14 wild-type embryo. More lateral cells have undergone uniform elongation. Ena is uniformly enriched at adherens junctions of leading edge cells (left, red). Actin forms a tight cable along the leading edge (middle, green). Ena and actin colocalize at adherens junctions as actin expands along the entire leading edge. (D) Stage 14 ablMZ mutant. Nonuniform localization of Ena and Actin persists. Cells with excess Ena (left, arrow) often accumulate excess Actin (middle, arrow), whereas cells with diminished Ena levels (left, bracket) have diminished levels of Actin (middle, bracket) Bars, 10 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2199330&req=5

fig4: Complete loss of Abl alters Ena and actin localization during dorsal closure. Lateral view. Embryos double-labeled with anti-Ena (red) and phalloidin (green), labeling F-actin. (A) Stage 13 wild-type embryo with leading edge cells initiating elongation. Ena (left, red) is enriched at vertices of cell–cell contact. Actin (middle, green) outlines all cell membranes and is beginning to accumulate at the leading edge. Actin and Ena colocalize at cell junctions. (B) Stage 13 ablMZ mutant. Ena (left, red) and Actin (middle, green) enrichment is not uniform at the leading edge. Both are enriched in some cells (arrows) and depleted in others (brackets). (C) Stage 14 wild-type embryo. More lateral cells have undergone uniform elongation. Ena is uniformly enriched at adherens junctions of leading edge cells (left, red). Actin forms a tight cable along the leading edge (middle, green). Ena and actin colocalize at adherens junctions as actin expands along the entire leading edge. (D) Stage 14 ablMZ mutant. Nonuniform localization of Ena and Actin persists. Cells with excess Ena (left, arrow) often accumulate excess Actin (middle, arrow), whereas cells with diminished Ena levels (left, bracket) have diminished levels of Actin (middle, bracket) Bars, 10 μm.
Mentions: The defects in cell morphology during dorsal closure in ablMZ mutants led us to examine localization of actin and of the Abl target Ena, an actin regulator during this process. In the initial stages of dorsal closure, as cells along the leading edge begin to elongate, Ena surrounds the cell membrane but is enriched at vertices of cell–cell contact and at adherens junctions of leading edge cells (Fig. 4 A, left, red). Actin localizes around the entire cell and begins to accumulate at the leading edge at this stage (Fig. 4 A, middle, green; Young et al., 1993). As closure proceeds, Ena accumulates at uniformly high levels in adherens junctions of leading edge cells (Fig. 4 C, left, red), while actin forms a uniform and tightly localized band along the leading edge (Fig. 4 D middle, green).

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