MRC National Institute for Medical Research, London
Science for Health
Regulating the extension and branching of axons in the cerebral cortex
24 April 2012
Research published by scientists from the University of Manchester and from NIMR has uncovered a mechanism that controls axonal extension and branching. The work is published in Nature Neuroscience.
The establishment of neuronal connectivity during cortical development depends on the proper growth and branching of axons. Errors in this process can lead to severe mental disorders such as: corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders. Recently, microRNAs have been found to be involved in axonal initiation in Caenorhabditis elegans, and in axon guidance in Xenopus laevis, but the question of whether miRNAs have additional roles in axonal development has remained largely unexplored.
miR-9, a highly conserved miRNA, has a well-established role in coordinating the neuronal proliferation and migration of neuronal precursors. The group of Nancy Papalopulu at University of Manchester, collaborating with Patricia Garcez and François Guillemot (pictured) in NIMR’s Division of Molecular Neurobiology, have sought to answer whether miR-9 has additional functions in differentiating neurons by examining its role in the development of projection neurons of the cerebral cortex in vivo.
They first identified the microtubule-associated protein 1b, Map1b, as a target that is repressed by miR-9 in neurons. Map1b is an important protein for microtubule stability. To determine whether its repression plays a role in axonal development, the researchers electroporated in utero a construct that specifically blocks miR-9 binding to Map1b. They found that this resulted in an increase in axonal length and a reduction in the number of axonal branches. A separate set of experiments showed that miR-9 acts downstream of brain-derived neurotrophic factor (BDNF).
This study has identified a new role for a microRNA in the developing nervous system, in regulation of axonal development downstream of BDNF signalling.
François Guillemot
Click image to view at full-size
Sections of electroporated cerebral cortex of mouse embryos. Axonal processes from neurons electroporated with eGFP (control) can be seen extending medially toward the midline. Axons co-electroporated with eGFP and the miR-9-Map1b interaction inhibitor Map1b-TP have grown further. The arrow indicates the end of the axonal tract.
Original article
Federico Dajas-Bailador, Boyan Bonev, Patricia Garcez, Peter Stanley, François Guillemot & Nancy Papalopulu (2012)
microRNA-9 regulates axon extension and branching by targeting Map1b in mouse cortical neurons
Nature Neuroscience, epub ahead of print. Publisher abstract
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