RT Journal Article
SR Electronic
T1 NGF Regulates the Expression of Axonal LINGO-1 to Inhibit Oligodendrocyte Differentiation and Myelination
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 220
OP 225
DO 10.1523/JNEUROSCI.4175-06.2007
VO 27
IS 1
A1 Lee, Xinhua
A1 Yang, Zhongshu
A1 Shao, Zhaohui
A1 Rosenberg, Sheila S.
A1 Levesque, Melissa
A1 Pepinsky, R. Blake
A1 Qiu, Mengsheng
A1 Miller, Robert H.
A1 Chan, Jonah R.
A1 Mi, Sha
YR 2007
UL http://www.jneurosci.org/content/27/1/220.abstract
AB Neurons and glia share a mutual dependence in establishing a functional relationship, and none is more evident than the process by which axons control myelination. Here, we identify LRR and Ig domain-containing, Nogo receptor-interacting protein (LINGO-1) as a potent axonal inhibitor of oligodendrocyte differentiation and myelination that is regulated by nerve growth factor and its cognate receptor TrkA in a dose-dependent manner. Whereas LINGO-1 expressed by oligodendrocyte progenitor cells was previously identified as an inhibitor of differentiation, we demonstrate that axonal expression of LINGO-1 inhibits differentiation with equal potency. Disruption of LINGO-1 on either cell type is sufficient to overcome the inhibitory action and promote differentiation and myelination, independent of axon diameter. Furthermore, these results were recapitulated in transgenic mice overexpressing the full length LINGO-1 under the neuronal promoter synapsin. Myelination was greatly inhibited in the presence of enforced axonal LINGO-1. The implications of these results relate specifically to the development of potential therapeutics targeting extrinsic growth factors that may regulate the axonal expression of modulators of oligodendrocyte development.