Polarized Expression of p75NTR Specifies Axons during Development and Adult Neurogenesis

Newly generated neurons initiate polarizing signals that specify a single axon and multiple dendrites, aprocess critical for patterning neuronal circuits invivo. Here, we report that the pan-neurotrophin receptor p75NTR is a polarity regulator that localizes asymmetrically in differentiating neurons in response to neurotrophins and is required for specification of the future axon. In cultured hippocampal neurons, local exposure to neurotrophins causes early accumulation of p75NTR into one undifferentiated neurite to specify axon fate. Moreover, knockout or knockdown of p75NTR results in failure to initiate an axon in newborn neurons upon cell-cycle exit invitro and in the developing cortex, as well as during adult hippocampal neurogenesis invivo. Hence, p75NTR governs neuronal polarity, determining pattern and assembly of neuronal circuits in adult hippocampus and cortical development.