PUBLICATION

The lh3 Glycosyltransferase Directs Target-Selective Peripheral Nerve Regeneration

Authors
Isaacman-Beck, J., Schneider, V., Franzini-Armstrong, C., Granato, M.
ID
ZDB-PUB-151110-8
Date
2015
Source
Neuron   88(4): 691-703 (Journal)
Registered Authors
Granato, Michael, Schneider, Valerie
Keywords
none
MeSH Terms
  • Glycosyltransferases/genetics*
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Nerve Tissue Proteins/metabolism
  • Nerve Regeneration/genetics*
  • Schwann Cells/metabolism*
  • Peripheral Nerve Injuries
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics*
  • Peripheral Nerves/physiology*
  • Motor Neurons/physiology*
  • Collagen Type IV/genetics
  • Animals
  • Axons/physiology*
(all 14)
PubMed
26549330 Full text @ Neuron
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.
Genes / Markers
Figures
Figure Gallery (11 images) / 2
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b393
    		Complex
    ml2TgTransgenic Insertion
      p164TgTransgenic Insertion
        p165TgTransgenic Insertion
          p166TgTransgenic Insertion
            p167TgTransgenic Insertion
              rw012TgTransgenic Insertion
                s510
                  		Point Mutation
                  tv205a
                    		Point Mutation
                    vu17TgTransgenic Insertion
                      1 - 10 of 12
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      No data available
                      Antibodies
                      No data available
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GFPEFGGFP
                      mKate2EFGmKate2
                      mRFPEFGmRFP
                      1 - 5 of 5
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                      Mapping
                      No data available
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                      Citation
                      Isaacman-Beck, J., Schneider, V., Franzini-Armstrong, C., Granato, M. (2015) The lh3 Glycosyltransferase Directs Target-Selective Peripheral Nerve Regeneration. Neuron. 88(4):691-703.