Neurotrophin-induced Polarized Expression of p75NTR...

February 8, 2013
2:30 p.m.

Neurotrophin-induced Polarized Expression of p75NTR Specifies Axons During Development and Adult Neurogenesis

A newly generated neuron initiates polarizing signals that specify a single axon and multiple dendrites, a process critical for patterning neuronal circuits in vivo.
Here, we report that the pan-neurotrophin receptor p75^NTR is a polarity regulator that localizes asymmetrically in differentiating neurons in response to neurotrophins and transduces polarity signals for specification of the futureaxon.
In cultured hippocampal neurons, local exposure to neurotrophins caused recruitment of p75^NTR and mPar-3 into one undifferentiated neurite,
nucleating a complex essential for axogenesis.
Disruption of p75^NTR subcellular localization, by knockout/down or ectopic expression, prevented asymmetric accumulation/activation of conserved cell-polarity signaling pathways at the axonal tip and resulted in failure to initiate an axon in newborn neurons upon cell cycle exit in vitro and in vivo.
Hence, p75NTR governs polarity in the developing cortex and adult hippocampus, determining pattern and assembly of neuronal circuits in these brain areas.