Polarized Expression of p75NTR Specifies Axons during Development and Adult Neurogenesis
Emanuela Zuccaro,
Matteo Bergami,
Beatrice Vignoli,
Guillaume Bony,
Brian A. Pierchala,
Spartaco Santi,
Laura Cancedda,
Marco Canossa
Affiliations
Emanuela Zuccaro
Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), via Morego 30, I-16163 Genoa, Italy
Matteo Bergami
Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), via Morego 30, I-16163 Genoa, Italy
Beatrice Vignoli
Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), via Morego 30, I-16163 Genoa, Italy
Guillaume Bony
Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), via Morego 30, I-16163 Genoa, Italy
Brian A. Pierchala
Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, 1011 N. University Avenue, Ann Arbor, MI 48109, USA
Spartaco Santi
National Research Council (CNR), Institute of Molecular Genetics (IGM)-Bologna, Laboratory of Muscoloskeletal Cell Biology, IOR, via di Barbiano1/10, I-40136 Bologna, Italy
Laura Cancedda
Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), via Morego 30, I-16163 Genoa, Italy
Marco Canossa
Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), via Morego 30, I-16163 Genoa, Italy
Newly 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:
