Abstract

Neuromesodermal Progenitors: Tracing the Origins of Neuromuscular Diseases

Mina Gouti, Group Leader, Max-Delbrück Center for Molecular Medicine

During embryonic development spinal cord motor neurons are generated with high precision along the rostral – caudal axis and establish connections with skeletal muscles to control movement. Previous studies have shown that motor neurons and muscles depend on each other for proper development and survival but until recently their generation was considered as independent events. Striking evidence coming from clonal lineage analysis experiments in the mouse embryo suggested that a common bipotent progenitor exists in vivo that can give descendants in both the spinal cord and paraxial mesoderm. These cells, called neuromesodermal progenitors (NMPs), reside in the caudal lateral epiblast region of the embryo and are important for axis elongation and correct tissue growth but have been largely overlooked in the stem cell field. Following the cues from mouse embryonic development we have recently succeeded in generating NMP cells in vitro from mouse and human pluripotent stem cells. The in vitro generation of these cells opens up new opportunities for the study and treatment of neuromuscular diseases as it gives unprecedented access to the simultaneous development of both neural and mesodermal cell types in the “dish”. Apart from a deeper understanding of spinal cord development, our novel culture system enables new promises for disease modeling and drug screening of incurable neuromuscular diseases such as Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA) and Muscular Dystrophy.