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Dcas supports cell polarization and cell-cell adhesion complexes in development.

Tikhmyanova N, Tulin AV, Roegiers F, Golemis EA - PLoS ONE (2010)

Bottom Line: Loss of Dcas had limited effect on embryonal development.However, we found that Dcas is an important modulator of the severity of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A.These results support an important role for Cas proteins in cell-cell adhesion signaling in development.

View Article: PubMed Central - PubMed

Affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.

ABSTRACT
Mammalian Cas proteins regulate cell migration, division and survival, and are often deregulated in cancer. However, the presence of four paralogous Cas family members in mammals (BCAR1/p130Cas, EFS/Sin1, NEDD9/HEF1/Cas-L, and CASS4/HEPL) has limited their analysis in development. We deleted the single Drosophila Cas gene, Dcas, to probe the developmental function of Dcas. Loss of Dcas had limited effect on embryonal development. However, we found that Dcas is an important modulator of the severity of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A. Strikingly, embryonic lethal Fak56D-Dcas double mutant embryos had extensive cell polarity defects, including mislocalization and reduced expression of E-cadherin. Further genetic analysis established that loss of Dcas modified the embryonal lethal phenotypes of embryos with mutations in E-cadherin (Shg) or its signaling partners p120- and beta-catenin (Arm). These results support an important role for Cas proteins in cell-cell adhesion signaling in development.

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Related in: MedlinePlus

Genetic interactions of Dcas with shg.A. Representative genetic cross of two double heterozygous parents (shgK03401 and Dcas1) to allow analysis of the viability of resulting progeny. Each row in the graph represents percentage of viable progeny of indicated genotype. B. Cuticle preparations of WT, shg2/shg2 and Dcas1/Dcas1;shg2/shg2 stage 16 embryos, viewed ventrally (panels i and iii), laterally (panel ii) and dorsally (panels iv–v). * indicates defects in head and ventral cuticle formation, respectively, arrows point to holes in ventral and dorsal cuticle. Genotypes and percentages of cuticles with indicated phenotypes are marked on top. Scale bar, 100 µm.
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pone-0012369-g006: Genetic interactions of Dcas with shg.A. Representative genetic cross of two double heterozygous parents (shgK03401 and Dcas1) to allow analysis of the viability of resulting progeny. Each row in the graph represents percentage of viable progeny of indicated genotype. B. Cuticle preparations of WT, shg2/shg2 and Dcas1/Dcas1;shg2/shg2 stage 16 embryos, viewed ventrally (panels i and iii), laterally (panel ii) and dorsally (panels iv–v). * indicates defects in head and ventral cuticle formation, respectively, arrows point to holes in ventral and dorsal cuticle. Genotypes and percentages of cuticles with indicated phenotypes are marked on top. Scale bar, 100 µm.

Mentions: We therefore next assessed genetic interactions between the Dcas1 allele and loss-of-function alleles of shotgun (shg2, encoding an unstable protein that is prone to degradation [53]; shgE17B, a genetic mutation producing a defective DE-cadherin; and shgK03401, produced by a P-element interruption of gene transcription) [54], and its functional partners armadillo (arm2, arm3, arm8,) and p120catenin (p120ctn308). Neither heterozygotic alleles of shg2, shgE17B p120ctn308 and arm2, nor double heterozygotes of Dcas1 and any of these genes produced visible phenotypes or reduced the emergence of adult flies (Figure 6 and Table 2). However, Dcas1/Dcas1 in combination with heterozygous shgK03401, arm3 or arm8, or homozygous p120ctn308, severely reduced viable adult progeny, as did combination of Dcas1/+ with p120ctn308/p120ctn308 (Figures 6A, 7A, 7B, and Table 2).


Dcas supports cell polarization and cell-cell adhesion complexes in development.

Tikhmyanova N, Tulin AV, Roegiers F, Golemis EA - PLoS ONE (2010)

Genetic interactions of Dcas with shg.A. Representative genetic cross of two double heterozygous parents (shgK03401 and Dcas1) to allow analysis of the viability of resulting progeny. Each row in the graph represents percentage of viable progeny of indicated genotype. B. Cuticle preparations of WT, shg2/shg2 and Dcas1/Dcas1;shg2/shg2 stage 16 embryos, viewed ventrally (panels i and iii), laterally (panel ii) and dorsally (panels iv–v). * indicates defects in head and ventral cuticle formation, respectively, arrows point to holes in ventral and dorsal cuticle. Genotypes and percentages of cuticles with indicated phenotypes are marked on top. Scale bar, 100 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2927436&req=5

pone-0012369-g006: Genetic interactions of Dcas with shg.A. Representative genetic cross of two double heterozygous parents (shgK03401 and Dcas1) to allow analysis of the viability of resulting progeny. Each row in the graph represents percentage of viable progeny of indicated genotype. B. Cuticle preparations of WT, shg2/shg2 and Dcas1/Dcas1;shg2/shg2 stage 16 embryos, viewed ventrally (panels i and iii), laterally (panel ii) and dorsally (panels iv–v). * indicates defects in head and ventral cuticle formation, respectively, arrows point to holes in ventral and dorsal cuticle. Genotypes and percentages of cuticles with indicated phenotypes are marked on top. Scale bar, 100 µm.
Mentions: We therefore next assessed genetic interactions between the Dcas1 allele and loss-of-function alleles of shotgun (shg2, encoding an unstable protein that is prone to degradation [53]; shgE17B, a genetic mutation producing a defective DE-cadherin; and shgK03401, produced by a P-element interruption of gene transcription) [54], and its functional partners armadillo (arm2, arm3, arm8,) and p120catenin (p120ctn308). Neither heterozygotic alleles of shg2, shgE17B p120ctn308 and arm2, nor double heterozygotes of Dcas1 and any of these genes produced visible phenotypes or reduced the emergence of adult flies (Figure 6 and Table 2). However, Dcas1/Dcas1 in combination with heterozygous shgK03401, arm3 or arm8, or homozygous p120ctn308, severely reduced viable adult progeny, as did combination of Dcas1/+ with p120ctn308/p120ctn308 (Figures 6A, 7A, 7B, and Table 2).

Bottom Line: Loss of Dcas had limited effect on embryonal development.However, we found that Dcas is an important modulator of the severity of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A.These results support an important role for Cas proteins in cell-cell adhesion signaling in development.

View Article: PubMed Central - PubMed

Affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.

ABSTRACT
Mammalian Cas proteins regulate cell migration, division and survival, and are often deregulated in cancer. However, the presence of four paralogous Cas family members in mammals (BCAR1/p130Cas, EFS/Sin1, NEDD9/HEF1/Cas-L, and CASS4/HEPL) has limited their analysis in development. We deleted the single Drosophila Cas gene, Dcas, to probe the developmental function of Dcas. Loss of Dcas had limited effect on embryonal development. However, we found that Dcas is an important modulator of the severity of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A. Strikingly, embryonic lethal Fak56D-Dcas double mutant embryos had extensive cell polarity defects, including mislocalization and reduced expression of E-cadherin. Further genetic analysis established that loss of Dcas modified the embryonal lethal phenotypes of embryos with mutations in E-cadherin (Shg) or its signaling partners p120- and beta-catenin (Arm). These results support an important role for Cas proteins in cell-cell adhesion signaling in development.

Show MeSH
Related in: MedlinePlus