N-Cadherin specifies first asymmetry in developing pyramidal neurons

The precise polarization and orientation of developing
neurons is essential for the correct wiring of the brain.
In pyramidal excitatory neurons, polarization begins with
the sprouting of opposite neurites, which later define
directed migration and axo-dendritic domains. We here
show that endogenous N-cadherin concentrates at one
pole of the newborn neuron, from where the first neurite
subsequently emerges. Ectopic N-cadherin is sufficient to
favour the place of appearance of the first neurite. The
Golgi and centrosome move towards this newly formed
morphological pole in a second step, which is regulated by
PI3K and the actin/microtubule cytoskeleton. Moreover,
loss of function experiments in vivo showed that developing
neurons with a non-functional N-cadherin misorient
their cell axis. These results show that polarization of
N-cadherin in the immediate post-mitotic stage is an
early and crucial mechanism in neuronal polarity.