The Adhesion Molecule-Characteristic HNK-1 Carbohydrate Contributes to Functional Recovery After Spinal Cord Injury in Adult Zebrafish

Ma, L., Shen, H.F., Shen, Y.Q., Schachner, M.
Molecular neurobiology   54(5): 3253-3263 (Journal)
Registered Authors
Schachner, Melitta
HNK-1 carbohydrate, HNK-1 glucuronyl transferase, HNK-1 sulfotransferase, Regeneration, Spinal cord injury, Zebrafish
MeSH Terms
  • Animals
  • Axons/drug effects
  • Axons/metabolism
  • Brain Stem/pathology
  • Cell Adhesion Molecules/metabolism*
  • Male
  • Morpholinos/pharmacology
  • Motor Activity/drug effects
  • Nerve Regeneration
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Recovery of Function*
  • Spinal Cord/metabolism
  • Spinal Cord/pathology
  • Spinal Cord Injuries/enzymology*
  • Spinal Cord Injuries/physiopathology*
  • Sulfotransferases/genetics
  • Sulfotransferases/metabolism*
  • Zebrafish/metabolism*
27086029 Full text @ Mol. Neurobiol.
The human natural killer cell antigen-1 (HNK-1) is functionally important in development, synaptic activity, and regeneration after injury in the nervous system of several mammalian species. It contains a sulfated glucuronic acid which is carried by neural adhesion molecules and expressed in nonmammalian species, including zebrafish, which, as opposed to mammals, spontaneously regenerate after injury in the adult. To evaluate HNK-1's role in recovery of function after spinal cord injury (SCI) of adult zebrafish, we assessed the effects of the two HNK-1 synthesizing enzymes, glucuronyl transferase and HNK-1 sulfotransferase. Expression of these two enzymes was increased at the messenger RNA (mRNA) level 11 days after injury in the brainstem nuclei that are capable of regrowth of severed axons, namely, the nucleus of medial longitudinal fascicle and intermediate reticular formation, but not at earlier time points after SCI. mRNA levels of glucuronyl transferase and sulfotransferase were increased in neurons, not only of these nuclei but also in the spinal cord caudal to the injury site at 11 days. Mauthner neurons which are not capable of regeneration did not show increased levels of enzyme mRNAs after injury. Reducing protein levels of the enzymes by application of anti-sense morpholinos resulted in reduction of locomotor recovery for glucuronyl transferase, but not for HNK-1 sulfotransferase. The combined results indicate that HNK-1 is upregulated in expression only in those neurons that are intrinsically capable of regeneration and contributes to regeneration after spinal cord injury in adult zebrafish in the absence of its sulfate moiety.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes