Modeling Motor Neuron Resilience in ALS Using Stem Cells.
IF: 7.294
Cited by: 24


Oculomotor neurons, which regulate eye movement, are resilient to degeneration in the lethal motor neuron disease amyotrophic lateral sclerosis (ALS). It would be highly advantageous if motor neuron resilience could be modeled in vitro. Toward this goal, we generated a high proportion of oculomotor neurons from mouse embryonic stem cells through temporal overexpression of PHOX2A in neuronal progenitors. We demonstrate, using electrophysiology, immunocytochemistry, and RNA sequencing, that in vitro-generated neurons are bona fide oculomotor neurons based on their cellular properties and similarity to their in vivo counterpart in rodent and man. We also show that in vitro-generated oculomotor neurons display a robust activation of survival-promoting Akt signaling and are more resilient to the ALS-like toxicity of kainic acid than spinal motor neurons. Thus, we can generate bona fide oculomotor neurons in vitro that display a resilience similar to that seen in vivo.


Gene Expression
LCM sequencing
Onuf’s nucleus
RNA sequencing
amyotrophic lateral sclerosis
neuronal vulnerability and resistance
oculomotor neurons
spinal motor neurons
stem cells

MeSH terms

Amyotrophic Lateral Sclerosis
Cell Differentiation
Cell Survival
Homeodomain Proteins
Motor Neurons
Mouse Embryonic Stem Cells
Proto-Oncogene Proteins c-akt
Signal Transduction


Allodi, Ilary
Nijssen, Jik
Benitez, Julio Aguila
Schweingruber, Christoph
Fuchs, Andrea
Bonvicini, Gillian
Cao, Ming
Kiehn, Ole
Hedlund, Eva

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