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Updated: Dec 11, 2025
Efficient Differentiation of Mouse Embryonic Stem Cells into Motor Neurons
Published on: June 9, 2012
Cdo Is Required for Efficient Motor Neuron Generation of Embryonic Stem Cells
Hyebeen Kim1,2, Seul-Yi Lee3,2, Hyeon-Ju Jeong1,2
1Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea.
Background And Objectives:
The directed differentiation of pluripotent stem cells into motor neurons is critical for the development of disease modelling and therapeutics to intervene degenerative motor neuron diseases. Cell surface receptor Cdo functions as a coreceptor for Sonic hedgehog (Shh) with Boc and Gas1 in the patterning of ventral spinal cord neurons including motor neurons. However, the discrete function of Cdo is not fully understood.
Methods And Results:
In this study, we examined the role of Cdo in motor neuron generation by utilizing in vitro differentiation of Cdo＋/＋ and Cdo-/- embryonic stem cells (ESCs). In response to Shh, Cdo-/- ESCs exhibited impaired expression of motor neuron specification markers while dorsal interneuron specification markers were significantly increased, compared to Cdo＋/＋ ESCs. Reactivation of Shh signalling pathway with Smoothened (Smo) agonist (SAG) restored motor neuron specification in Cdo-/- ESCs. In addition, electrophysiological analysis revealed the immature electrical features of Cdo-/- ESCs-derived neurons which was restored by SAG.
Conclusions:
Taken together, these data suggest that Cdo as a Shh coreceptor is required for the induction of motor neuron generation by fully activating Shh signalling pathway and provide additional insights into the biology of motor neuron development.
Insights
Cell surface receptor Cdo is essential for generating motor neurons from pluripotent stem cells. Its absence impairs motor neuron development, but Sonic hedgehog (Shh) pathway reactivation can restore this process.
Area of Science:
- Developmental Neuroscience
- Stem Cell Biology
- Molecular Biology
Background:
- Motor neuron generation is crucial for modeling and treating neurodegenerative diseases.
- Cell surface receptor Cdo acts as a coreceptor for Sonic hedgehog (Shh) in neural patterning.
- The specific role of Cdo in motor neuron development remains incompletely understood.
Purpose of the Study:
- To investigate the function of Cdo in the directed differentiation of motor neurons from embryonic stem cells.
- To elucidate the mechanism by which Cdo influences Shh signaling in motor neuron specification.
Main Methods:
- Utilized in vitro differentiation of Cdo-wildtype (Cdo+/+) and Cdo-knockout (Cdo-/-) embryonic stem cells (ESCs).
- Analyzed motor neuron and interneuron specification markers in response to Shh signaling.
- Examined the effect of Smoothened agonist (SAG) on motor neuron differentiation in Cdo-/- ESCs.
- Performed electrophysiological analysis on differentiated neurons.
Main Results:
- Cdo-/- ESCs showed impaired motor neuron marker expression and increased dorsal interneuron markers upon Shh stimulation compared to Cdo+/+ ESCs.
- Reactivation of the Shh pathway with SAG restored motor neuron specification in Cdo-/- ESCs.
- Electrophysiological analysis indicated immature neuronal features in Cdo-/- ESCs-derived neurons, which were rescued by SAG treatment.
Conclusions:
- Cdo functions as a critical Shh coreceptor required for efficient motor neuron induction.
- Full activation of the Shh signaling pathway by Cdo is essential for motor neuron generation.
- These findings provide novel insights into the molecular mechanisms governing motor neuron development.
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