PUBLICATION

The Fz-Dsh Planar Cell Polarity Pathway Induces Oriented Cell Division via Mud/NuMA in Drosophila and Zebrafish

Authors
Segalen, M., Johnston, C.A., Martin, C.A., Dumortier, J.G., Prehoda, K.E., David, N.B., Doe, C.Q., and Bellaiche, Y.
ID
ZDB-PUB-101122-5
Date
2010
Source
Developmental Cell   19(5): 740-752 (Journal)
Registered Authors
David, Nicholas
Keywords
none
MeSH Terms
  • Cell Polarity/physiology*
  • Drosophila Proteins/genetics
  • Drosophila Proteins/metabolism*
  • Animals
  • Drosophila melanogaster*/cytology
  • Drosophila melanogaster*/physiology
  • Recombinant Fusion Proteins/genetics
  • Recombinant Fusion Proteins/metabolism
  • Frizzled Receptors/genetics
  • Frizzled Receptors/metabolism*
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Guanine Nucleotide Dissociation Inhibitors/genetics
  • Guanine Nucleotide Dissociation Inhibitors/metabolism
  • Spindle Apparatus/metabolism
  • Embryo, Nonmammalian/anatomy & histology
  • Embryo, Nonmammalian/physiology
  • Dyneins/metabolism
  • Nuclear Matrix-Associated Proteins/genetics
  • Nuclear Matrix-Associated Proteins/metabolism*
  • Humans
  • Cell Lineage
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Gastrulation
  • Signal Transduction/physiology
  • Cell Division/physiology*
  • Cell Line
  • Phosphoproteins/genetics
  • Phosphoproteins/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish*/anatomy & histology
  • Zebrafish*/physiology
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
PubMed
21074723 Full text @ Dev. Cell
Abstract
The Frizzled receptor and Dishevelled effector regulate mitotic spindle orientation in both vertebrates and invertebrates, but how Dishevelled orients the mitotic spindle is unknown. Using the Drosophila S2 cell "induced polarity" system, we find that Dishevelled cortical polarity is sufficient to orient the spindle and that Dishevelled's DEP domain mediates this function. This domain binds a C-terminal domain of Mud (the Drosophila NuMA ortholog), and Mud is required for Dishevelled-mediated spindle orientation. In Drosophila, Frizzled-Dishevelled planar cell polarity (PCP) orients the sensory organ precursor (pI) spindle along the anterior-posterior axis. We show that Dishevelled and Mud colocalize at the posterior cortex of pI, Mud localization at the posterior cortex requires Dsh, and Mud loss-of-function randomizes spindle orientation. During zebrafish gastrulation, the Wnt11-Frizzled-Dishevelled PCP pathway orients spindles along the animal-vegetal axis, and reducing NuMA levels disrupts spindle orientation. Overall, we describe a Frizzled-Dishevelled-NuMA pathway that orients division from Drosophila to vertebrates.
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