CELL BIOLOGY OF THE NEURON Polarity ... - Tavernarakis Lab

Cell Biology of the Neuron: Polarity, Plasticity and Regeneration, Crete 2011
Establishment of Neuronal Polarity
Carlos G. Dotti
Department of Neuroscience, Centro de Biología Molecular Severo Ochoa,
Universidad Autónoma de Madrid, Madrid, Spain
VIB Department of Molecular and Developmental Genetics.K.U.Leuven
Department of Human Genetics, Leuven, Belgium
In a recent work we showed that, in Drosophila neurons undergoing
differentiation in vivo, the first membrane deformation occurs at 3.6 minutes after
precursor division. Using conventional genetic expression analysis, we observed
that adhesion complex components (Bazooka/PAR-3, cadherin-catenin) marks the
place where the first deformation later occurs, appearing with a clustered
distribution at 2.8 minutes after division (eg. 1 minute before morphological
deformation). We also observed that the upstream molecule PIP2, known to be
required for cadherin-catenin spatial restriction during epithelia polarization,
becomes clustered at the site of future apical neurite formation by 0.7 minutes
after division (eg. 3 minutes before morphological deformation). RhoA, whose
activity is required for PIP2 generation and cadherin-catenin clustering, is
clustered to the pole of future apical neurite from the time of cytokinesis, thus at
time 0. To investigate to which extent these concentration differences could be
sufficient to determine polarity we used a mathematical modeling approach. In
addition to its intrinsic value, this was needed because i) it is not possible to
knockdown any of the above molecules in the precursor cell (the consequence is
division arrest) and ii) it is not possible to determine the effect of suppression in
the newborn neuron due to the rapid onset of polarization. Mathematical
modelling allowed to demonstrate: 1) that a polarized domain can form
spontaneously in a newborn cell as consequence of a change in the equilibrium
(i.e. concentration) state and 2) that occurrence of growth from this pole is
enough to trigger the occurrence of a second growth domain at the exact opposite
pole. Thus, the in vivo data provided insights into the molecular hierarchy
accompanying polarization, revealing the existence of conservative mechanisms
with the apical-basal polarization of epithelia, and the mathematical modelling
proved that any polarized change in the steady-state equilibrium can suffice to
determine the site where polarization will occur and the occurrence of growth at
the opposite pole.
Presented by: Dotti, Carlos G.
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