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Cell Rep. 2014 Apr 10;7(1):138-52. doi: 10.1016/j.celrep.2014.02.039. Epub 2014 Mar 27.

Polarized expression of p75(NTR) specifies axons during development and adult neurogenesis.

Author information

1
Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), via Morego 30, I-16163 Genoa, Italy.
2
Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), via Morego 30, I-16163 Genoa, Italy; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University Hospital of Cologne, Joseph-Stelzmann-Strasse 26, Cologne, Germany.
3
Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, 1011 N. University Avenue, Ann Arbor, MI 48109, USA.
4
National Research Council (CNR), Institute of Molecular Genetics (IGM)-Bologna, Laboratory of Muscoloskeletal Cell Biology, IOR, via di Barbiano1/10, I-40136 Bologna, Italy.
5
Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), via Morego 30, I-16163 Genoa, Italy. Electronic address: laura.cancedda@iit.it.
6
Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), via Morego 30, I-16163 Genoa, Italy; European Brain Research Institute (EBRI) "Rita Levi-Montalcini," via del Fosso di Fiorano 64/65, I-00143 Rome, Italy. Electronic address: marco.canossa@iit.it.

Abstract

VIDEO ABSTRACT:

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 p75(NTR) 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 p75(NTR) into one undifferentiated neurite to specify axon fate. Moreover, knockout or knockdown of p75(NTR) 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, p75(NTR) governs neuronal polarity, determining pattern and assembly of neuronal circuits in adult hippocampus and cortical development.

PMID:
24685135
DOI:
10.1016/j.celrep.2014.02.039
[Indexed for MEDLINE]
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