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Regulation of cytoskeletal organization and junctional remodeling by the atypical cadherin Fat.

Abstract
The atypical cadherin Fat is a conserved regulator of planar cell polarity, but the mechanisms by which Fat controls cell shape and tissue structure are not well understood. Here, we show that Fat is required for the planar polarized organization of actin denticle precursors, adherens junction proteins and microtubules in the epidermis of the late Drosophila embryo. In wild-type embryos, spatially regulated cell-shape changes and rearrangements organize cells into highly aligned columns. Junctional remodeling is suppressed at dorsal and ventral cell boundaries, where adherens junction proteins accumulate. By contrast, adherens junction proteins fail to accumulate to the wild-type extent and all cell boundaries are equally engaged in junctional remodeling in fat mutants. The effects of loss of Fat on cell shape and junctional localization, but not its role in denticle organization, are recapitulated by mutations in Expanded, an upstream regulator of the conserved Hippo pathway, and mutations in Hippo and Warts, two kinases in the Hippo kinase cascade. However, the cell shape and planar polarity defects in fat mutants are not suppressed by removing the transcriptional co-activator Yorkie, suggesting that these roles of Fat are independent of Yorkie-mediated transcription. The effects of Fat on cell shape, junctional remodeling and microtubule localization are recapitulated by expression of activated Notch. These results demonstrate that cell shape, junctional localization and cytoskeletal planar polarity in the Drosophila embryo are regulated by a common signal provided by the atypical cadherin Fat and suggest that Fat influences tissue organization through its role in polarized junctional remodeling.
AuthorsEmily Marcinkevicius, Jennifer A Zallen
JournalDevelopment (Cambridge, England) (Development) Vol. 140 Issue 2 Pg. 433-43 (Jan 15 2013) ISSN: 1477-9129 [Electronic] England
PMID23250217 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Actins
  • Cadherins
  • Cell Adhesion Molecules
  • Drosophila Proteins
  • Frizzled Receptors
  • Receptors, Notch
  • ft protein, Drosophila
  • fz protein, Drosophila
Topics
  • Actins (metabolism)
  • Animals
  • Cadherins (metabolism)
  • Cell Adhesion
  • Cell Adhesion Molecules (metabolism)
  • Drosophila (embryology)
  • Drosophila Proteins (metabolism)
  • Drosophila melanogaster
  • Frizzled Receptors (metabolism)
  • Gene Expression Regulation, Developmental
  • Immunohistochemistry (methods)
  • Microtubules (metabolism)
  • Models, Genetic
  • Mutation
  • Receptors, Notch (metabolism)
  • Time Factors

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