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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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ablMZ mutants have defects in epithelial morphogenesis. Cuticle preparations, anterior up. In A–D, dorsal is to the right. (A) Wild-type. (B–D) The range of phenotypes in abl4 maternal/zygotic mutants, a similar range is observed in abl1 . (B) Approximately 7% of ablMZ mutants have head involution defects and completely fail to germband retract. (C) ∼14% of ablMZ mutants partially fail to germband retract and have variable dorsal closure defects. Note the dorsal hole (arrow). (D) Approximately 67% of ablMZ mutants have dorsal closure defects. (E) Wild-type dorsal hair pattern. (F) Misaligned dorsal hairs in ablMZ mutant.
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fig2: ablMZ mutants have defects in epithelial morphogenesis. Cuticle preparations, anterior up. In A–D, dorsal is to the right. (A) Wild-type. (B–D) The range of phenotypes in abl4 maternal/zygotic mutants, a similar range is observed in abl1 . (B) Approximately 7% of ablMZ mutants have head involution defects and completely fail to germband retract. (C) ∼14% of ablMZ mutants partially fail to germband retract and have variable dorsal closure defects. Note the dorsal hole (arrow). (D) Approximately 67% of ablMZ mutants have dorsal closure defects. (E) Wild-type dorsal hair pattern. (F) Misaligned dorsal hairs in ablMZ mutant.

Mentions: We then examined whether Abl plays a role in epithelial development that is obscured by maternally contributed Abl. We first looked at the cuticle, secreted by the epidermal epithelium. ablMZ mutants exhibit defects in three morphogenetic processes, all of which require orchestrated cell shape changes and cell migration: germband retraction, head involution, and dorsal closure (Table II). Approximately 7% of ablMZ mutants completely fail to germband retract or complete head involution (Fig. 2 B), whereas ∼14% exhibit partial germband retraction and dorsal closure defects (Fig. 2 C). Approximately 67% of ablMZ mutants have more subtle defects in dorsal closure (Fig. 2, D and F), whereas ∼12% are wild-type in appearance or have minor head involution defects. In contrast, abl maternal mutants that inherit a paternal wild-type abl gene are rescued to normal embryogenesis and adulthood; most hatching larvae are wild-type whereas 5% have slight defects in germband retraction and dorsal patterning. Previous work revealed that certain Abl functions require kinase activity, whereas others do not (Henkemeyer et al., 1990). We found that maternal Abl's role in morphogenesis requires kinase activity, as both the embryonic phenotype and adult viability are rescued by a kinase-active Abl transgene but not by a kinase-dead version (Table I; unpublished data).


Abelson kinase regulates epithelial morphogenesis in Drosophila.

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

ablMZ mutants have defects in epithelial morphogenesis. Cuticle preparations, anterior up. In A–D, dorsal is to the right. (A) Wild-type. (B–D) The range of phenotypes in abl4 maternal/zygotic mutants, a similar range is observed in abl1 . (B) Approximately 7% of ablMZ mutants have head involution defects and completely fail to germband retract. (C) ∼14% of ablMZ mutants partially fail to germband retract and have variable dorsal closure defects. Note the dorsal hole (arrow). (D) Approximately 67% of ablMZ mutants have dorsal closure defects. (E) Wild-type dorsal hair pattern. (F) Misaligned dorsal hairs in ablMZ mutant.
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Related In: Results  -  Collection

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fig2: ablMZ mutants have defects in epithelial morphogenesis. Cuticle preparations, anterior up. In A–D, dorsal is to the right. (A) Wild-type. (B–D) The range of phenotypes in abl4 maternal/zygotic mutants, a similar range is observed in abl1 . (B) Approximately 7% of ablMZ mutants have head involution defects and completely fail to germband retract. (C) ∼14% of ablMZ mutants partially fail to germband retract and have variable dorsal closure defects. Note the dorsal hole (arrow). (D) Approximately 67% of ablMZ mutants have dorsal closure defects. (E) Wild-type dorsal hair pattern. (F) Misaligned dorsal hairs in ablMZ mutant.
Mentions: We then examined whether Abl plays a role in epithelial development that is obscured by maternally contributed Abl. We first looked at the cuticle, secreted by the epidermal epithelium. ablMZ mutants exhibit defects in three morphogenetic processes, all of which require orchestrated cell shape changes and cell migration: germband retraction, head involution, and dorsal closure (Table II). Approximately 7% of ablMZ mutants completely fail to germband retract or complete head involution (Fig. 2 B), whereas ∼14% exhibit partial germband retraction and dorsal closure defects (Fig. 2 C). Approximately 67% of ablMZ mutants have more subtle defects in dorsal closure (Fig. 2, D and F), whereas ∼12% are wild-type in appearance or have minor head involution defects. In contrast, abl maternal mutants that inherit a paternal wild-type abl gene are rescued to normal embryogenesis and adulthood; most hatching larvae are wild-type whereas 5% have slight defects in germband retraction and dorsal patterning. Previous work revealed that certain Abl functions require kinase activity, whereas others do not (Henkemeyer et al., 1990). We found that maternal Abl's role in morphogenesis requires kinase activity, as both the embryonic phenotype and adult viability are rescued by a kinase-active Abl transgene but not by a kinase-dead version (Table I; unpublished data).

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