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 differentiation of and embryonic stem cells (ESCs). In response to Shh, ESCs exhibited impaired expression of motor neuron specification markers while dorsal interneuron specification markers were significantly increased, compared to ESCs. Reactivation of Shh signalling pathway with Smoothened (Smo) agonist (SAG) restored motor neuron specification in ESCs. In addition, electrophysiological analysis revealed the immature electrical features of 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691856PMC
http://dx.doi.org/10.15283/ijsc20037DOI Listing

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