Motoneuron development influences dorsal root ganglia survival and Schwann cell development in a vertebrate model of spinal muscular atrophy

Hao, L.T., Phan, D.Q., Jontes, J.D., Beattie, C.E.
Human molecular genetics   24(2): 346-60 (Journal)
Registered Authors
Beattie, Christine, Jontes, James
MeSH Terms
  • Animals
  • Axons/metabolism
  • Cell Proliferation
  • Cell Survival*
  • Disease Models, Animal*
  • Ganglia, Spinal/growth & development*
  • Ganglia, Spinal/metabolism
  • Humans
  • Motor Neurons/cytology*
  • Motor Neurons/metabolism
  • Muscular Atrophy, Spinal/genetics
  • Muscular Atrophy, Spinal/metabolism
  • Muscular Atrophy, Spinal/physiopathology*
  • Schwann Cells/cytology*
  • Schwann Cells/metabolism
  • Survival of Motor Neuron 1 Protein/genetics
  • Survival of Motor Neuron 1 Protein/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/growth & development
  • Zebrafish*/metabolism
25180019 Full text @ Hum. Mol. Genet.
Low levels of the survival motor neuron protein (SMN) cause the disease spinal muscular atrophy (SMA). A primary characteristic of this disease is motoneuron dysfunction and paralysis. Understanding why motoneurons are affected by low levels of this protein will lend insight into this disease and to motoneuron biology in general. Motoneurons in zebrafish smn mutants develop abnormally however it is unclear where Smn is needed for motoneuron development since it is a ubiquitously expressed protein. We have addressed this issue by expressing human SMN in motoneurons in zebrafish maternal-zygotic (mz) smn mutants. Firstly, we demonstrate that SMN is present in axons, but only during the period of robust motor axon outgrowth. We also conclusively demonstrate that SMN acts cell autonomously in motoneurons for proper motoneuron development. This includes the formation of both axonal and dendritic branches. Analysis of the peripheral nervous system revealed that Schwann cells and dorsal root ganglia (DRG) neurons developed abnormally in mz-smn mutants. Schwann cells did not wrap axons tightly and had expanded nodes of Ranvier. The majority of DRG neurons had abnormally short peripheral axons and later many of them failed to divide and died. Expressing SMN just in motoneurons rescued both of these cell types showing that their failure to develop was secondary to the developmental defects in motoneurons. Driving SMN just in motoneurons did not increase survival of the animal suggesting that SMN is needed for motoneuron development and motor circuitry, but that SMN in other cells types factors into survival.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes