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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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Dorsal closure is substantially slowed in ablMZ mutants. Dorsal view of embryos expressing moesin-GFP, anterior to the right. Time is in minutes. Insets in (B, H, and N) display actin-rich filopodia extending from amnioserosa or leading edge cells. (A–D) Wild-type embryo at 30 min intervals during dorsal closure. (A) The leading edge of the dorsal closure front is uniformly enriched in actin. Lateral epithelial sheets elongate uniformly. (B) 30 min. Amnioserosa cells are undergoing apical constriction and the embryo is zipping together at the anterior and posterior ends (arrows). (C) 60 min. Amnioserosa cells have constricted apically and remain in the same plane of focus as the lateral epithelial sheets. (D) 90 min. Dorsal closure is complete. (E–K) ablMZ mutant. The amnioserosa cells in E are comparable in surface area to the wild-type in A. (F–H) As closure progresses, amnioserosa cells constrict and lateral epithelial cells elongate, but dorsal closure is delayed relative to wild-type (compare D and H). If one matches embryos based on the length of the leading edge (compare A and G), closure is still delayed. This embryo took >4 h to complete closure (K). (L–R) A different ablMZ mutant at higher magnification, illustrating the folding-under of the leading edge and failure to complete closure. (S) Cross-section diagram depicting one interpretation of the defects of ablMZ mutants. In wild-type embryos, the rate at which lateral cells elongate, the sheets migrate, and amnioserosa cells constrict are tightly coordinated. In ablMZ mutants, the leading edge folds under the more lateral epidermis, perhaps because leading edge cells migrate too slowly or amnioserosa cell constriction is slowed (these events are likely coupled), forcing the sheet to fold under. Time-lapse videos supplementing this figure are available at http://www.jcb.org/cgi/content/full/jcb.200105102/DC1. Bars, 25 μm.
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fig5: Dorsal closure is substantially slowed in ablMZ mutants. Dorsal view of embryos expressing moesin-GFP, anterior to the right. Time is in minutes. Insets in (B, H, and N) display actin-rich filopodia extending from amnioserosa or leading edge cells. (A–D) Wild-type embryo at 30 min intervals during dorsal closure. (A) The leading edge of the dorsal closure front is uniformly enriched in actin. Lateral epithelial sheets elongate uniformly. (B) 30 min. Amnioserosa cells are undergoing apical constriction and the embryo is zipping together at the anterior and posterior ends (arrows). (C) 60 min. Amnioserosa cells have constricted apically and remain in the same plane of focus as the lateral epithelial sheets. (D) 90 min. Dorsal closure is complete. (E–K) ablMZ mutant. The amnioserosa cells in E are comparable in surface area to the wild-type in A. (F–H) As closure progresses, amnioserosa cells constrict and lateral epithelial cells elongate, but dorsal closure is delayed relative to wild-type (compare D and H). If one matches embryos based on the length of the leading edge (compare A and G), closure is still delayed. This embryo took >4 h to complete closure (K). (L–R) A different ablMZ mutant at higher magnification, illustrating the folding-under of the leading edge and failure to complete closure. (S) Cross-section diagram depicting one interpretation of the defects of ablMZ mutants. In wild-type embryos, the rate at which lateral cells elongate, the sheets migrate, and amnioserosa cells constrict are tightly coordinated. In ablMZ mutants, the leading edge folds under the more lateral epidermis, perhaps because leading edge cells migrate too slowly or amnioserosa cell constriction is slowed (these events are likely coupled), forcing the sheet to fold under. Time-lapse videos supplementing this figure are available at http://www.jcb.org/cgi/content/full/jcb.200105102/DC1. Bars, 25 μm.

Mentions: During dorsal closure in living wild-type embryos, the leading edge becomes uniformly enriched in actin as leading edge cells elongate (Fig. 5 A). Amnioserosa cells, the large squamous cells exposed on the dorsal surface of the embryo, undergo apical constriction (Kiehart et al., 2000), decreasing in surface area throughout closure (Fig. 5, A–D). Finally, as the lateral epithelial sheets migrate toward one another, closure is initiated at the anterior and posterior ends of the opening (Fig. 5 B, arrows) and the sheets zip together from the ends (Fig. 5, A–D) (Jacinto et al., 2000). Once the cells initiate elongation and the front is enriched in actin, dorsal closure is completed in a little over 1.5 h.


Abelson kinase regulates epithelial morphogenesis in Drosophila.

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

Dorsal closure is substantially slowed in ablMZ mutants. Dorsal view of embryos expressing moesin-GFP, anterior to the right. Time is in minutes. Insets in (B, H, and N) display actin-rich filopodia extending from amnioserosa or leading edge cells. (A–D) Wild-type embryo at 30 min intervals during dorsal closure. (A) The leading edge of the dorsal closure front is uniformly enriched in actin. Lateral epithelial sheets elongate uniformly. (B) 30 min. Amnioserosa cells are undergoing apical constriction and the embryo is zipping together at the anterior and posterior ends (arrows). (C) 60 min. Amnioserosa cells have constricted apically and remain in the same plane of focus as the lateral epithelial sheets. (D) 90 min. Dorsal closure is complete. (E–K) ablMZ mutant. The amnioserosa cells in E are comparable in surface area to the wild-type in A. (F–H) As closure progresses, amnioserosa cells constrict and lateral epithelial cells elongate, but dorsal closure is delayed relative to wild-type (compare D and H). If one matches embryos based on the length of the leading edge (compare A and G), closure is still delayed. This embryo took >4 h to complete closure (K). (L–R) A different ablMZ mutant at higher magnification, illustrating the folding-under of the leading edge and failure to complete closure. (S) Cross-section diagram depicting one interpretation of the defects of ablMZ mutants. In wild-type embryos, the rate at which lateral cells elongate, the sheets migrate, and amnioserosa cells constrict are tightly coordinated. In ablMZ mutants, the leading edge folds under the more lateral epidermis, perhaps because leading edge cells migrate too slowly or amnioserosa cell constriction is slowed (these events are likely coupled), forcing the sheet to fold under. Time-lapse videos supplementing this figure are available at http://www.jcb.org/cgi/content/full/jcb.200105102/DC1. Bars, 25 μm.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199330&req=5

fig5: Dorsal closure is substantially slowed in ablMZ mutants. Dorsal view of embryos expressing moesin-GFP, anterior to the right. Time is in minutes. Insets in (B, H, and N) display actin-rich filopodia extending from amnioserosa or leading edge cells. (A–D) Wild-type embryo at 30 min intervals during dorsal closure. (A) The leading edge of the dorsal closure front is uniformly enriched in actin. Lateral epithelial sheets elongate uniformly. (B) 30 min. Amnioserosa cells are undergoing apical constriction and the embryo is zipping together at the anterior and posterior ends (arrows). (C) 60 min. Amnioserosa cells have constricted apically and remain in the same plane of focus as the lateral epithelial sheets. (D) 90 min. Dorsal closure is complete. (E–K) ablMZ mutant. The amnioserosa cells in E are comparable in surface area to the wild-type in A. (F–H) As closure progresses, amnioserosa cells constrict and lateral epithelial cells elongate, but dorsal closure is delayed relative to wild-type (compare D and H). If one matches embryos based on the length of the leading edge (compare A and G), closure is still delayed. This embryo took >4 h to complete closure (K). (L–R) A different ablMZ mutant at higher magnification, illustrating the folding-under of the leading edge and failure to complete closure. (S) Cross-section diagram depicting one interpretation of the defects of ablMZ mutants. In wild-type embryos, the rate at which lateral cells elongate, the sheets migrate, and amnioserosa cells constrict are tightly coordinated. In ablMZ mutants, the leading edge folds under the more lateral epidermis, perhaps because leading edge cells migrate too slowly or amnioserosa cell constriction is slowed (these events are likely coupled), forcing the sheet to fold under. Time-lapse videos supplementing this figure are available at http://www.jcb.org/cgi/content/full/jcb.200105102/DC1. Bars, 25 μm.
Mentions: During dorsal closure in living wild-type embryos, the leading edge becomes uniformly enriched in actin as leading edge cells elongate (Fig. 5 A). Amnioserosa cells, the large squamous cells exposed on the dorsal surface of the embryo, undergo apical constriction (Kiehart et al., 2000), decreasing in surface area throughout closure (Fig. 5, A–D). Finally, as the lateral epithelial sheets migrate toward one another, closure is initiated at the anterior and posterior ends of the opening (Fig. 5 B, arrows) and the sheets zip together from the ends (Fig. 5, A–D) (Jacinto et al., 2000). Once the cells initiate elongation and the front is enriched in actin, dorsal closure is completed in a little over 1.5 h.

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