Abstract

Locomotion results from the interaction between muscles and the nervous system. Dysfunction of such cells results in deadly diseases such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Neuromuscular diseases often show regional selectivity but the underlying reasons remain obscure due to the lack of a suitable human model system. We have recently used human pluripotent stem cell derived axial stem cells, the building blocks of the posterior body, to simultaneously generate spinal cord neurons and skeletal muscle cells that self-organize in 3D to generate neuromuscular organoids (NMOs). NMOs contain functional neuromuscular junctions supported by terminal Schwann cells. They contract and develop central pattern generator-like neuronal circuits (Martins et al, Cell Stem Cell, 2020). We are currently applying NMOs to study the early development of the human neuromuscular system and to model neuromuscular diseases. This approach promises to uncover the sequence of events and provide greater insight into the mechanisms that lead to specific diseases by tackling previously inaccessible features of neuromuscular junction biology.