PUBLICATION

Sonic hedgehog is a polarized signal for motor neuron regeneration in adult zebrafish

Authors
Reimer, M.M., Kuscha, V., Wyatt, C., Sörensen, I., Frank, R.E., Knüwer, M., Becker, T., and Becker, C.G.
ID
ZDB-PUB-091215-32
Date
2009
Source
The Journal of neuroscience : the official journal of the Society for Neuroscience   29(48): 15073-15082 (Journal)
Registered Authors
Becker, Catherina G., Becker, Thomas, Frank, Rebecca E., Kuscha, Veronika, Reimer, Michell M., Wyatt, Cameron
Keywords
none
MeSH Terms
  • Transcription Factors/genetics
  • Cell Proliferation
  • Green Fluorescent Proteins/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Nerve Regeneration/drug effects
  • Nerve Regeneration/physiology*
  • Recovery of Function/drug effects
  • Recovery of Function/genetics
  • Disease Models, Animal
  • Hedgehog Proteins/genetics
  • Hedgehog Proteins/physiology*
  • Nerve Tissue Proteins/genetics
  • Veratrum Alkaloids/pharmacology
  • RNA, Messenger/metabolism
  • Signal Transduction/genetics
  • Signal Transduction/physiology*
  • Motor Neurons/drug effects
  • Motor Neurons/physiology*
  • Lysine/analogs & derivatives
  • Lysine/metabolism
  • Gene Expression Regulation/drug effects
  • Gene Expression Regulation/genetics
  • Gene Expression Regulation/physiology*
  • Neuroglia/metabolism
  • Spinal Cord Injuries/pathology
  • Spinal Cord Injuries/physiopathology
  • Zebrafish
  • Statistics, Nonparametric
  • Cell Polarity/genetics
  • Cell Polarity/physiology*
  • Animals, Genetically Modified
  • Animals
PubMed
19955358 Full text @ J. Neurosci.
Abstract
In contrast to mammals, the spinal cord of adult zebrafish has the capacity to reinitiate generation of motor neurons after a lesion. Here we show that genes involved in motor neuron development, i.e., the ventral morphogen sonic hedgehog a (shha), as well as the transcription factors nkx6.1 and pax6, together with a Tg(olig2:egfp) transgene, are expressed in the unlesioned spinal cord of adult zebrafish. Expression is found in ependymoradial glial cells lining the central canal in ventrodorsal positions that match expression domains of these genes in the developing neural tube. Specifically, Tg(olig2:egfp)(+) ependymoradial glial cells, the adult motor neuron progenitors (pMNs), coexpress Nkx6.1 and Pax6, thus defining an adult pMN-like zone. shha is expressed in distinct ventral ependymoradial glial cells. After a lesion, expression of all these genes is strongly increased, while relative spatial expression domains are maintained. In addition, expression of the hedgehog (hh) receptors patched1 and smoothened becomes detectable in ependymoradial glial cells including those of the pMN-like zone. Cyclopamine-induced knock down of hh signaling significantly reduces ventricular proliferation and motor neuron regeneration. Expression of indicator genes for the FGF and retinoic acid signaling pathways was also increased in the lesioned spinal cord. This suggests that a subclass of ependymoradial glial cells retain their identity as motor neuron progenitors into adulthood and are capable of reacting to a sonic hedgehog signal and potentially other developmental signals with motor neuron regeneration after a spinal lesion.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping