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://dx.doi.org/10.15283/ijsc20037 | DOI Listing |
J Neurophysiol
January 2025
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.
Parkinson's disease (PD) is a prevalent and challenging neurodegenerative disorder, and may involve impaired autophagy. Nuclear factor erythroid-2-related factor 2 (Nrf2) is crucial for regulating autophagy-related genes, maintaining cellular homeostasis. Electroacupuncture (EA), a complementary and alternative therapy for PD, has gained widespread clinical application.
View Article and Find Full Text PDFFront Chem
December 2024
Department of Algology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Introduction: Compression of the nerve root by a lumbar disc herniation can cause radiating pain in the lower limbs, and the nerve root decompression treatment may leave some patients with motor dysfunction and reduced sensory function. Studies have shown that nerve growth factor (NGF) can promote nerve growth and repair, but high doses, long duration, and immune response have become bottlenecks of its clinical application.
Methods: To overcome this obstacle, we developed Prussian blue (PBs) nanoparticles with the bio-delivery function and antioxidant effects of nanoenzymes.
Nature
January 2025
Department of Neurobiology and Behavior, Cornell University, Ithaca, NY, USA.
Accurate goal-directed behaviour requires the sense of touch to be integrated with information about body position and ongoing motion. Behaviours such as chewing, swallowing and speech critically depend on precise tactile events on a rapidly moving tongue, but neural circuits for dynamic touch-guided tongue control are unknown. Here, using high-speed videography, we examined three-dimensional lingual kinematics as mice drank from a water spout that unexpectedly changed position during licking, requiring re-aiming in response to subtle contact events on the left, centre or right surface of the tongue.
View Article and Find Full Text PDFNat Rev Neurol
January 2025
Edinburgh Medical School, Biomedical Sciences, University of Edinburgh, Edinburgh, UK.
The motor neuron disease amyotrophic lateral sclerosis (ALS) is a devastating condition with limited treatment options. The past few years have witnessed a ramping up of translational ALS research, offering the prospect of disease-modifying therapies. Although breakthroughs using gene-targeted approaches have shown potential to treat patients with specific disease-causing mutations, the applicability of such therapies remains restricted to a minority of individuals.
View Article and Find Full Text PDFEur J Neurol
January 2025
Genetics Department, Institut de Recerca Sant Pau (IR SANT PAU), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Background And Purpose: Pathogenic variants in the RYR1 gene have been associated with a variety of conditions, ranging from congenital myopathy to adult manifestations. Our aim was to characterize the p.Leu2286Val variant in 17 Basque patients, to accurately determine its correlation with clinical features and to explore the possible founder effect of the variant.
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