Anthrax toxin receptor 2a controls mitotic spindle positioning

I Castanon1, L Abrami, L Holtzer

  • 1Departments of Biochemistry and Molecular Biology, Sciences II, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.

Nature Cell Biology
|December 4, 2012
PubMed

Insights

Oriented cell division guides tissue development. This study reveals how anthrax toxin receptor 2a (Antxr2a) and actin filaments align cell division planes along the animal-vegetal axis during zebrafish gastrulation.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Oriented cell division is crucial for tissue morphogenesis.
  • The Wnt/planar cell polarity (Wnt/PCP) pathway is known to orient mitosis in various developmental systems.
  • The precise mechanism by which Wnt signaling controls mitotic orientation remains unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism by which Wnt signaling orients the mitotic plane in dorsal epiblast cells during zebrafish gastrulation.
  • To identify key proteins involved in the Wnt-dependent orientation of cell division.

Main Methods:

  • Confocal microscopy to visualize protein localization and F-actin dynamics.
  • Biochemical assays to study protein-protein interactions.
  • Genetic manipulation to assess the function of key proteins in vivo.

Main Results:

  • Anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap aligned with the animal-vegetal (A-V) axis, predicting the division plane.
  • Filamentous actin (F-actin) also forms an A-V polarized cap, dependent on Wnt/PCP, RhoA, and Rock2.
  • Antxr2a interacts with actin and RhoA, activating zDia2 and exerting torque on the spindle to align it with the A-V axis.

Conclusions:

  • Antxr2a acts as a Wnt-dependent polarized determinant that orients cell division.
  • The Wnt/PCP pathway, through Antxr2a, RhoA, and zDia2, provides a mechanism for aligning mitotic spindles with the embryonic A-V axis.
  • This provides critical insights into the regulation of oriented cell division during tissue development.

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