Polarized Expression of p75NTR Specifies Axons during Development and Adult Neurogenesis

• p75NTR represents a direct link between neurotrophins and polarity regulators
• Neurotrophin/p75NTR generates a positive-feedback loop to determine axon fate
• p75NTR governs pattern and assembly of neuronal circuits in vivo

SummaryNewly generated neurons initiate 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 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 in vitro and in the developing cortex, as well as during adult hippocampal neurogenesis in vivo. Hence, p75NTR governs neuronal polarity, determining pattern and assembly of neuronal circuits in adult hippocampus and cortical development.Video Abstract To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (72404 K)

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