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The lh3 Glycosyltransferase Directs Target-Selective Peripheral Nerve Regeneration.

Abstract：

:Functional PNS regeneration requires injured axons to return to their original synaptic targets, yet the mechanisms underlying target-selective regeneration have remained elusive. Using live-cell imaging in zebrafish we find that regenerating motor axons exhibit a strong preference for their original muscle territory and that axons probe both correct and incorrect trajectories extensively before selecting their original path. We show that this process requires the glycosyltransferase lh3 and that post-injury expression of lh3 in Schwann cells is sufficient to restore target-selective regeneration. Moreover, we demonstrate that Schwann cells neighboring the transection site express the lh3 substrate collagen4a5 and that during regeneration collagen4a5 destabilizes axons probing inappropriate trajectories to ensure target-selective regeneration, possibly through the axonal repellant slit1a. Our results demonstrate that selective ECM components match subpopulations of regenerating axons with their original targets and reveal a previously unappreciated mechanism that conveys synaptic target selection to regenerating axons in vivo. VIDEO ABSTRACT.

journal_name

Neuron

journal_title

Neuron

authors

Isaacman-Beck J,Schneider V,Franzini-Armstrong C,Granato M

doi

10.1016/j.neuron.2015.10.004

subject

Has Abstract

pub_date

2015-11-18 00:00:00

pages

691-703

issue

4

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(15)00870-3

journal_volume

88

pub_type

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