Developmental loss of NT-3 in vivo results in reduced levels of

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Glia. 2008 Feb;56(3):306-17.

Developmental loss of NT-3 in vivo results in reduced levels of

myelin-specific proteins, a reduced extent of myelination and

increased apoptosis of Schwann cells.

Woolley AG, Tait KJ, Hurren BJ, Fisher L, Sheard PW, Duxson MJ.

Department of Pathology, Dunedin School of Medicine, University of

Otago, Dunedin, New Zealand.

This work investigates the role of NT-3 in peripheral myelination.

Recent articles, based in vitro, propose that NT-3 acting through its

high-affinity receptor TrkC may act to inhibit myelin formation by

enhancing Schwann cell motility and/or migration. Here, we

investigate this hypothesis in vivo by examining myelination

formation in NT-3 mutant mice. On the day of birth, soon after the

onset of myelination, axons showed normal ensheathment by Schwann

cells, no change in the proportion of axons which had begun to

myelinate, and no change in either myelin thickness or number of

myelin lamellae. However in postnatal day 21 mice, when myelination

is substantially complete, we observed an unexpected reduction in

mRNA and protein levels for MAG and P(0), and in myelin thickness.

This is the opposite result to that predicted from previous in vitro

studies, where removal of an inhibitory NT-3 signal would have been

expected to enhance myelination. These results suggest that, in vivo,

the importance of NT-3 as a major support factor for Schwann cells

(Meier et al., (1999) J Neurosci 19:3847-3859) over-rides its

potential role as an myelin inhibitor, with the net effect that loss

of NT-3 results in degradation of Schwann cell functions, including

myelination. In support of this idea, Schwann cells of NT-3 null

mutants showed increased expression of activated caspase-3. Finally,

we observed significant reduction in width of the Schwann cell

periaxonal collar in NT-3 mutant animals suggesting that loss of NT-3

and resulting reduction in MAG levels may alter signaling at the axon-

glial interface.