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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 fail to undergo coordinated changes in cell shape during dorsal closure. Embryos labeled with antiphosphotyrosine. Anterior is to the left. (A–E) Wild-type at progressively later stages of dorsal closure. (A–C) Lateral views. (D and E) Dorsal views. (A) Leading edge cells have begun to uniformly elongate (arrow). (B and C) Successive lateral cell rows uniformly elongate (arrow). (D) Lateral epithelial sheets zip together. (E) Closure is complete, with lateral epithelial cells evenly matched at the midline (arrow). (F–J) ablMZ mutants at progressively later stages of dorsal closure. (F–H) Lateral and (I–J) dorsal views. (F) Leading edge cells do not elongate uniformly (arrow). Some cells have broadened or constricted leading edges (arrowheads). (G and H) Lateral cells have begun to elongate, but do so nonuniformly (arrow). Some cells have broadened or narrowed leading edges (arrowheads). Other groups of cells completely fail to elongate (asterisks). (I) ablMZ mutants that proceeded through dorsal closure. Small groups of cells have still completely failed to change shape (asterisks). (J) ablMZ mutant that completed closure. Epithelial sheets often fail to align properly at the midline (arrow). (K and L) Some ablMZ mutants initiate dorsal closure even though they have not completed germband retraction. Cell shape defects are also seen in these embryos (arrows). (M and N) armXP33 mutants have cell shape defects similar to ablMZ mutants. Cells fail to elongate uniformly (arrow) and have broadened or narrowed leading edges (arrowheads). (O) Cell shape defects in ablMZ mutants are not caused by multinucleate cells. ablMZ, double-labeled with antiphosphotyrosine and with propidium iodide, labeling nuclei. Mononucleate cells have defects in shape (arrow). Bars: (A–J and L–O) 10 μm; (K) 50 μm.
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fig3: ablMZ mutants fail to undergo coordinated changes in cell shape during dorsal closure. Embryos labeled with antiphosphotyrosine. Anterior is to the left. (A–E) Wild-type at progressively later stages of dorsal closure. (A–C) Lateral views. (D and E) Dorsal views. (A) Leading edge cells have begun to uniformly elongate (arrow). (B and C) Successive lateral cell rows uniformly elongate (arrow). (D) Lateral epithelial sheets zip together. (E) Closure is complete, with lateral epithelial cells evenly matched at the midline (arrow). (F–J) ablMZ mutants at progressively later stages of dorsal closure. (F–H) Lateral and (I–J) dorsal views. (F) Leading edge cells do not elongate uniformly (arrow). Some cells have broadened or constricted leading edges (arrowheads). (G and H) Lateral cells have begun to elongate, but do so nonuniformly (arrow). Some cells have broadened or narrowed leading edges (arrowheads). Other groups of cells completely fail to elongate (asterisks). (I) ablMZ mutants that proceeded through dorsal closure. Small groups of cells have still completely failed to change shape (asterisks). (J) ablMZ mutant that completed closure. Epithelial sheets often fail to align properly at the midline (arrow). (K and L) Some ablMZ mutants initiate dorsal closure even though they have not completed germband retraction. Cell shape defects are also seen in these embryos (arrows). (M and N) armXP33 mutants have cell shape defects similar to ablMZ mutants. Cells fail to elongate uniformly (arrow) and have broadened or narrowed leading edges (arrowheads). (O) Cell shape defects in ablMZ mutants are not caused by multinucleate cells. ablMZ, double-labeled with antiphosphotyrosine and with propidium iodide, labeling nuclei. Mononucleate cells have defects in shape (arrow). Bars: (A–J and L–O) 10 μm; (K) 50 μm.

Mentions: To compare cell shape changes and cell migration in wild-type and ablMZ mutants, we examined embryos during dorsal closure, using antiphosphotyrosine to label both adherens junctions and the leading edge actin cable. As wild-type dorsal closure initiates, leading edge cells elongate uniformly along the dorsal-ventral axis, perpendicular to the leading edge (Fig. 3 A, arrow). As closure proceeds, successive rows of cells lateral to the leading edge also uniformly elongate (Fig. 3, B and C, arrow). The lateral epithelial sheets eventually meet at the dorsal midline, and cells intercalate with one another, making the dorsal surface a continuous epithelial sheet with little midline discontinuity (Figs. 3, D and E, arrow).


Abelson kinase regulates epithelial morphogenesis in Drosophila.

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

ablMZ mutants fail to undergo coordinated changes in cell shape during dorsal closure. Embryos labeled with antiphosphotyrosine. Anterior is to the left. (A–E) Wild-type at progressively later stages of dorsal closure. (A–C) Lateral views. (D and E) Dorsal views. (A) Leading edge cells have begun to uniformly elongate (arrow). (B and C) Successive lateral cell rows uniformly elongate (arrow). (D) Lateral epithelial sheets zip together. (E) Closure is complete, with lateral epithelial cells evenly matched at the midline (arrow). (F–J) ablMZ mutants at progressively later stages of dorsal closure. (F–H) Lateral and (I–J) dorsal views. (F) Leading edge cells do not elongate uniformly (arrow). Some cells have broadened or constricted leading edges (arrowheads). (G and H) Lateral cells have begun to elongate, but do so nonuniformly (arrow). Some cells have broadened or narrowed leading edges (arrowheads). Other groups of cells completely fail to elongate (asterisks). (I) ablMZ mutants that proceeded through dorsal closure. Small groups of cells have still completely failed to change shape (asterisks). (J) ablMZ mutant that completed closure. Epithelial sheets often fail to align properly at the midline (arrow). (K and L) Some ablMZ mutants initiate dorsal closure even though they have not completed germband retraction. Cell shape defects are also seen in these embryos (arrows). (M and N) armXP33 mutants have cell shape defects similar to ablMZ mutants. Cells fail to elongate uniformly (arrow) and have broadened or narrowed leading edges (arrowheads). (O) Cell shape defects in ablMZ mutants are not caused by multinucleate cells. ablMZ, double-labeled with antiphosphotyrosine and with propidium iodide, labeling nuclei. Mononucleate cells have defects in shape (arrow). Bars: (A–J and L–O) 10 μm; (K) 50 μm.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: ablMZ mutants fail to undergo coordinated changes in cell shape during dorsal closure. Embryos labeled with antiphosphotyrosine. Anterior is to the left. (A–E) Wild-type at progressively later stages of dorsal closure. (A–C) Lateral views. (D and E) Dorsal views. (A) Leading edge cells have begun to uniformly elongate (arrow). (B and C) Successive lateral cell rows uniformly elongate (arrow). (D) Lateral epithelial sheets zip together. (E) Closure is complete, with lateral epithelial cells evenly matched at the midline (arrow). (F–J) ablMZ mutants at progressively later stages of dorsal closure. (F–H) Lateral and (I–J) dorsal views. (F) Leading edge cells do not elongate uniformly (arrow). Some cells have broadened or constricted leading edges (arrowheads). (G and H) Lateral cells have begun to elongate, but do so nonuniformly (arrow). Some cells have broadened or narrowed leading edges (arrowheads). Other groups of cells completely fail to elongate (asterisks). (I) ablMZ mutants that proceeded through dorsal closure. Small groups of cells have still completely failed to change shape (asterisks). (J) ablMZ mutant that completed closure. Epithelial sheets often fail to align properly at the midline (arrow). (K and L) Some ablMZ mutants initiate dorsal closure even though they have not completed germband retraction. Cell shape defects are also seen in these embryos (arrows). (M and N) armXP33 mutants have cell shape defects similar to ablMZ mutants. Cells fail to elongate uniformly (arrow) and have broadened or narrowed leading edges (arrowheads). (O) Cell shape defects in ablMZ mutants are not caused by multinucleate cells. ablMZ, double-labeled with antiphosphotyrosine and with propidium iodide, labeling nuclei. Mononucleate cells have defects in shape (arrow). Bars: (A–J and L–O) 10 μm; (K) 50 μm.
Mentions: To compare cell shape changes and cell migration in wild-type and ablMZ mutants, we examined embryos during dorsal closure, using antiphosphotyrosine to label both adherens junctions and the leading edge actin cable. As wild-type dorsal closure initiates, leading edge cells elongate uniformly along the dorsal-ventral axis, perpendicular to the leading edge (Fig. 3 A, arrow). As closure proceeds, successive rows of cells lateral to the leading edge also uniformly elongate (Fig. 3, B and C, arrow). The lateral epithelial sheets eventually meet at the dorsal midline, and cells intercalate with one another, making the dorsal surface a continuous epithelial sheet with little midline discontinuity (Figs. 3, D and E, arrow).

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