A novel role for the pan-neurotrophin receptor p75NTR in axonal specification
Recent research led by Dr. Marco Canossa at the European Brain Research Institute (EBRI) and Laura Cancedda at the Italian Institute of Technology (IIT) has uncovered a novel role for the pan-neurotrophins receptor p75 in the development of newborn neurons.
The work conducted by Canossa’s group focused on growth factors, the neurotrophins which have the potentials to elicit early polarity programs for axonal specification and regulation of neural circuit assembly. Specifically, they found that neurotrophins critically contribute to the early steps of neural circuit assembly initiating the growth of an axon at the expense of dendritic growth. Moreover, polarized expression of the pan-neurotrophins receptor p75 orients axogenesis and the assembly of neuronal circuits. Hence, the pan-neurotrophin receptor p75 is a polarity regulator that localizes asymmetrically in differentiating neurons in response to neurotrophins and is required for specification of the future axon. Ultimately, p75 governs axogenesis determining pattern and assembly of neuronal circuits in cortical developmentand and adult hippocampus in vivo.
The prospect of regulating axogenesis by neurotrophins is relevant for circuit modification and its therapeutic benefit. Indeed, deregulation of axogenesis during embryonic development leads to inborn neurological disorders, while deregulation during adulthood is associated to nearly every neurodegenerative disease, such as Alzheimer's Disease. A crucial aspect in this attempt concerns the correct axon’s initiation and growth to avoid atypical connections that may be unfavorable to normal circuit function.
The highly regulated axonal specification by the pan-neurotrophins receptor p75 provides an important lesson on the challenges to develop further strategies for the refinement of functionally neuronal circuits.
Watch the video abstract related to this work published in Cell Reports on March 27, 2014. In this video, Marco Canossa and Laura Cancedda discuss their findings on the polarized expression of p75NTR during development and adult neurogenesis (https://www.youtube.com/watch?v=PjaVAQ1jiz8).