Int J Stem Cells.  2020 Nov;13(3):342-352. 10.15283/ijsc20037.

Cdo Is Required for Efficient Motor Neuron Generation of Embryonic Stem Cells

Affiliations
  • 1Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
  • 2Department of Physiology, Sungkyunkwan University School of Medicine, Suwon, Korea
  • 3Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, Korea

Abstract

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.

Keyword

Cdo; Shh coreceptors; Shh signalling pathway
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