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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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Mutations in ena enhance arm's dorsal closure defects. Cuticle preparations, anterior up. (A) Wild-type. (B) armH8.6 mutants have segment polarity defects due to defects in Wingless signaling (arrowhead), but head involution and dorsal closure are normal. (C) ena210/enaGC1. (D) armH8.6/Y; enaGC1/enaGC1. Note strong defects in dorsal closure and head involution (arrow), with no change in the segment polarity phenotype (arrowhead). (E) armYD35 mutants have a dorsal hole (arrows), as well strong segment polarity defects. (F) The dorsal side of armYD35; ena210/ena210 embryos is completely open (arrows).
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fig7: Mutations in ena enhance arm's dorsal closure defects. Cuticle preparations, anterior up. (A) Wild-type. (B) armH8.6 mutants have segment polarity defects due to defects in Wingless signaling (arrowhead), but head involution and dorsal closure are normal. (C) ena210/enaGC1. (D) armH8.6/Y; enaGC1/enaGC1. Note strong defects in dorsal closure and head involution (arrow), with no change in the segment polarity phenotype (arrowhead). (E) armYD35 mutants have a dorsal hole (arrows), as well strong segment polarity defects. (F) The dorsal side of armYD35; ena210/ena210 embryos is completely open (arrows).

Mentions: Our genetic experiments suggest that Ena misregulation plays a role in the defects in morphogenesis of ablMZ mutants (Table I). As Ena localizes to adherens junctions, we wondered whether it might work with adherens junction components during morphogenesis. We thus looked for genetic interactions between ena and arm. We crossed females heterozygous for mutations in both arm and ena to males heterozygous for ena. Both arm and ena are embryonic lethal; as arm is on the X-chromosome, we expect 43% of the dead progeny to be arm mutant, 43% to be ena mutant, and 14% to be arm; ena double mutants. Null alleles of Arm have dorsal closure defects, due to a combination of affects on cell adhesion and Wg signaling (McEwen et al., 2000), whereas weaker arm alleles do not have dorsal closure defects. We first tested the weakest allele of arm, armH8.6, in which dorsal closure is normal, although segment polarity is affected (Fig. 7 B). Although ena homozygotes are embryonic lethal, most of the dead embryos only have mild defects in head involution (Gertler et al., 1990; Fig. 7 C). A small fraction (∼5%) have dorsal pattern defects indicative of mild problems in dorsal closure. When we generated armH8.6; enaGC1 double mutants, we found strong synergistic defects in both head involution and dorsal closure (Fig. 7 D; Table III). Mutations in ena also enhance the dorsal closure defects of the stronger arm mutants armXM19, armXP33 (unpublished data), and armYD35 (Fig. 7, E and F; Table III), though it is difficult to rule out the possibility that these interactions are simply additive.


Abelson kinase regulates epithelial morphogenesis in Drosophila.

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

Mutations in ena enhance arm's dorsal closure defects. Cuticle preparations, anterior up. (A) Wild-type. (B) armH8.6 mutants have segment polarity defects due to defects in Wingless signaling (arrowhead), but head involution and dorsal closure are normal. (C) ena210/enaGC1. (D) armH8.6/Y; enaGC1/enaGC1. Note strong defects in dorsal closure and head involution (arrow), with no change in the segment polarity phenotype (arrowhead). (E) armYD35 mutants have a dorsal hole (arrows), as well strong segment polarity defects. (F) The dorsal side of armYD35; ena210/ena210 embryos is completely open (arrows).
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Related In: Results  -  Collection

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fig7: Mutations in ena enhance arm's dorsal closure defects. Cuticle preparations, anterior up. (A) Wild-type. (B) armH8.6 mutants have segment polarity defects due to defects in Wingless signaling (arrowhead), but head involution and dorsal closure are normal. (C) ena210/enaGC1. (D) armH8.6/Y; enaGC1/enaGC1. Note strong defects in dorsal closure and head involution (arrow), with no change in the segment polarity phenotype (arrowhead). (E) armYD35 mutants have a dorsal hole (arrows), as well strong segment polarity defects. (F) The dorsal side of armYD35; ena210/ena210 embryos is completely open (arrows).
Mentions: Our genetic experiments suggest that Ena misregulation plays a role in the defects in morphogenesis of ablMZ mutants (Table I). As Ena localizes to adherens junctions, we wondered whether it might work with adherens junction components during morphogenesis. We thus looked for genetic interactions between ena and arm. We crossed females heterozygous for mutations in both arm and ena to males heterozygous for ena. Both arm and ena are embryonic lethal; as arm is on the X-chromosome, we expect 43% of the dead progeny to be arm mutant, 43% to be ena mutant, and 14% to be arm; ena double mutants. Null alleles of Arm have dorsal closure defects, due to a combination of affects on cell adhesion and Wg signaling (McEwen et al., 2000), whereas weaker arm alleles do not have dorsal closure defects. We first tested the weakest allele of arm, armH8.6, in which dorsal closure is normal, although segment polarity is affected (Fig. 7 B). Although ena homozygotes are embryonic lethal, most of the dead embryos only have mild defects in head involution (Gertler et al., 1990; Fig. 7 C). A small fraction (∼5%) have dorsal pattern defects indicative of mild problems in dorsal closure. When we generated armH8.6; enaGC1 double mutants, we found strong synergistic defects in both head involution and dorsal closure (Fig. 7 D; Table III). Mutations in ena also enhance the dorsal closure defects of the stronger arm mutants armXM19, armXP33 (unpublished data), and armYD35 (Fig. 7, E and F; Table III), though it is difficult to rule out the possibility that these interactions are simply additive.

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