Sonic hedgehog is a polarized signal for motor neuron regeneration in adult zebrafish.
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.
Reimer
Michell M
MM
Centre for Neuroregeneration, School of Biomedical Sciences, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, United Kingdom.
Kuscha
Veronika
V
Wyatt
Cameron
C
Sörensen
Inga
I
Frank
Rebecca E
RE
Knüwer
Martin
M
Becker
Thomas
T
Becker
Catherina G
CG
D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology*; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D012333:RNA, Messenger / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics; D014704:Veratrum Alkaloids / Q000494:pharmacology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D008239:Lysine; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D012333:RNA, Messenger; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D029961:Zebrafish Proteins; C531385:Mnx1 protein, zebrafish; C524053:Shha protein, zebrafish; C465361:olig2 protein, zebrafish; C013411:biocytin; C000541:cyclopamine