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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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Levels of junctional Arm and α-catenin are reduced in ablMZ mutants. Embryos labeled with anti-Arm (A–D), anti–α-catenin (E and F), anti–DE-cadherin (G and H), antiphosphotyrosine (I and J), anti-Neurotactin (K and L), anti-Crumbs (M and N), and anti-Coracle (O-P). (A and B) Stage 8. (C and D) Stage 14. (A and C) Wild-type. Arm localizes to adherens junctions. (B and D) ablMZ mutants. Arm accumulates at reduced levels in adherens junctions. (E and F) Stage 13. (E) Wild-type. α-catenin localizes to adherens junctions. (F) ablMZ mutant. α-catenin accumulates at reduced levels in adherens junctions. (G–J) Stage 13. DE-cadherin localizes to adherens junctions, without striking differences in localization or levels between wild-type (G) and ablMZ mutants (H). Phosphotyrosine localizes to adherens junctions, without noticeable differences between wild-type (I) and ablMZ mutants (J). (K and L) Stage 11. Neurotactin localizes to the baso-lateral membrane without noticeable differences between wild-type (K) and ablMZ mutants (L). (M and N) Cross-sectional views, Stage 11. Crumbs localizes to the apical membrane of epithelial cells without striking differences between wild-type (M) and ablMZ mutants (N). (O and P) Stage 13. Coracle localizes to septate junctions with no striking difference in levels between wild-type (O) and ablMZ mutants (P). Bar, 10 μm.
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fig9: Levels of junctional Arm and α-catenin are reduced in ablMZ mutants. Embryos labeled with anti-Arm (A–D), anti–α-catenin (E and F), anti–DE-cadherin (G and H), antiphosphotyrosine (I and J), anti-Neurotactin (K and L), anti-Crumbs (M and N), and anti-Coracle (O-P). (A and B) Stage 8. (C and D) Stage 14. (A and C) Wild-type. Arm localizes to adherens junctions. (B and D) ablMZ mutants. Arm accumulates at reduced levels in adherens junctions. (E and F) Stage 13. (E) Wild-type. α-catenin localizes to adherens junctions. (F) ablMZ mutant. α-catenin accumulates at reduced levels in adherens junctions. (G–J) Stage 13. DE-cadherin localizes to adherens junctions, without striking differences in localization or levels between wild-type (G) and ablMZ mutants (H). Phosphotyrosine localizes to adherens junctions, without noticeable differences between wild-type (I) and ablMZ mutants (J). (K and L) Stage 11. Neurotactin localizes to the baso-lateral membrane without noticeable differences between wild-type (K) and ablMZ mutants (L). (M and N) Cross-sectional views, Stage 11. Crumbs localizes to the apical membrane of epithelial cells without striking differences between wild-type (M) and ablMZ mutants (N). (O and P) Stage 13. Coracle localizes to septate junctions with no striking difference in levels between wild-type (O) and ablMZ mutants (P). Bar, 10 μm.

Mentions: ablMZ mutants had reduced levels of Arm in adherens junctions. This was first noticeable in germband-extended embryos (Fig. 9, A and B) and became more pronounced during dorsal closure in wild-type (Fig. 9, C and D). Cross-sectional views suggest that the decrease in Arm at adherens junctions is not due to mislocalization of Arm to a different place in the cell (unpublished data), and we also think it is unlikely to be solely due to the alterations in cell shape in the mutant. Given these effects on Arm, we analyzed other adherens junction components. α-catenin, a protein that links Arm to the actin cytoskeleton, also showed reduced accumulation in adherens junctions (Fig. 9, E and F). The localization of both Arm and α-catenin was more variable in paternally rescued embryos, with reduction in some individuals but not others (unpublished data). The accumulation of DE-cadherin at junctions also may be slightly reduced in ablMZ mutants (Figs. 9, G and H), but this effect was less pronounced than that on Arm or α-catenin. We also examined several other cortical or membrane markers. The accumulation of phosphotyrosine in adherens junctions (Fig. 9, I and J), Coracle at septate junctions (PFig. 9, O and P), Neurotactin at the basolateral membrane (Fig. 9, K and L), and Crumbs at the apical membrane (Fig. 9, M and N) were only slightly reduced or unaffected. In doing these experiments, we also observed that the defects in cell shape in ablMZ mutants are not restricted to dorsal closure. We observed defects in the uniform apical constrictions that occur in cells along the ventral midline (Fig. 9, A and B). Defects in cell shape changes and cell migration could also explain the observed defects in germband retraction.


Abelson kinase regulates epithelial morphogenesis in Drosophila.

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

Levels of junctional Arm and α-catenin are reduced in ablMZ mutants. Embryos labeled with anti-Arm (A–D), anti–α-catenin (E and F), anti–DE-cadherin (G and H), antiphosphotyrosine (I and J), anti-Neurotactin (K and L), anti-Crumbs (M and N), and anti-Coracle (O-P). (A and B) Stage 8. (C and D) Stage 14. (A and C) Wild-type. Arm localizes to adherens junctions. (B and D) ablMZ mutants. Arm accumulates at reduced levels in adherens junctions. (E and F) Stage 13. (E) Wild-type. α-catenin localizes to adherens junctions. (F) ablMZ mutant. α-catenin accumulates at reduced levels in adherens junctions. (G–J) Stage 13. DE-cadherin localizes to adherens junctions, without striking differences in localization or levels between wild-type (G) and ablMZ mutants (H). Phosphotyrosine localizes to adherens junctions, without noticeable differences between wild-type (I) and ablMZ mutants (J). (K and L) Stage 11. Neurotactin localizes to the baso-lateral membrane without noticeable differences between wild-type (K) and ablMZ mutants (L). (M and N) Cross-sectional views, Stage 11. Crumbs localizes to the apical membrane of epithelial cells without striking differences between wild-type (M) and ablMZ mutants (N). (O and P) Stage 13. Coracle localizes to septate junctions with no striking difference in levels between wild-type (O) and ablMZ mutants (P). Bar, 10 μm.
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fig9: Levels of junctional Arm and α-catenin are reduced in ablMZ mutants. Embryos labeled with anti-Arm (A–D), anti–α-catenin (E and F), anti–DE-cadherin (G and H), antiphosphotyrosine (I and J), anti-Neurotactin (K and L), anti-Crumbs (M and N), and anti-Coracle (O-P). (A and B) Stage 8. (C and D) Stage 14. (A and C) Wild-type. Arm localizes to adherens junctions. (B and D) ablMZ mutants. Arm accumulates at reduced levels in adherens junctions. (E and F) Stage 13. (E) Wild-type. α-catenin localizes to adherens junctions. (F) ablMZ mutant. α-catenin accumulates at reduced levels in adherens junctions. (G–J) Stage 13. DE-cadherin localizes to adherens junctions, without striking differences in localization or levels between wild-type (G) and ablMZ mutants (H). Phosphotyrosine localizes to adherens junctions, without noticeable differences between wild-type (I) and ablMZ mutants (J). (K and L) Stage 11. Neurotactin localizes to the baso-lateral membrane without noticeable differences between wild-type (K) and ablMZ mutants (L). (M and N) Cross-sectional views, Stage 11. Crumbs localizes to the apical membrane of epithelial cells without striking differences between wild-type (M) and ablMZ mutants (N). (O and P) Stage 13. Coracle localizes to septate junctions with no striking difference in levels between wild-type (O) and ablMZ mutants (P). Bar, 10 μm.
Mentions: ablMZ mutants had reduced levels of Arm in adherens junctions. This was first noticeable in germband-extended embryos (Fig. 9, A and B) and became more pronounced during dorsal closure in wild-type (Fig. 9, C and D). Cross-sectional views suggest that the decrease in Arm at adherens junctions is not due to mislocalization of Arm to a different place in the cell (unpublished data), and we also think it is unlikely to be solely due to the alterations in cell shape in the mutant. Given these effects on Arm, we analyzed other adherens junction components. α-catenin, a protein that links Arm to the actin cytoskeleton, also showed reduced accumulation in adherens junctions (Fig. 9, E and F). The localization of both Arm and α-catenin was more variable in paternally rescued embryos, with reduction in some individuals but not others (unpublished data). The accumulation of DE-cadherin at junctions also may be slightly reduced in ablMZ mutants (Figs. 9, G and H), but this effect was less pronounced than that on Arm or α-catenin. We also examined several other cortical or membrane markers. The accumulation of phosphotyrosine in adherens junctions (Fig. 9, I and J), Coracle at septate junctions (PFig. 9, O and P), Neurotactin at the basolateral membrane (Fig. 9, K and L), and Crumbs at the apical membrane (Fig. 9, M and N) were only slightly reduced or unaffected. In doing these experiments, we also observed that the defects in cell shape in ablMZ mutants are not restricted to dorsal closure. We observed defects in the uniform apical constrictions that occur in cells along the ventral midline (Fig. 9, A and B). Defects in cell shape changes and cell migration could also explain the observed defects in germband retraction.

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