We use human and mouse pluripotent stem cells (PSCs) to model embryo development in vitro and understand the mechanisms that regulate cell fate decisions during neuromuscular system development. During embryonic development spinal cord motor neurons are generated with high precision along the anterior-posterior (AP) axis and establish connections with skeletal muscles to control movement. Previous studies have shown that development and survival of motor neurons and muscles depend on each other but until recently their generation were 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 to 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 ignored 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”.
Our focus is to understand how these two tissues are generated and interact in space and time during human development. This will allow us to unravel the mechanisms of human embryo development and evaluate how defects in the early development of these tissues may predispose to disease in adult life. To address these questions we are using gain and loss of gene function approaches (crispr/cas9), next-generation sequencing technologies (single cell RNA-seq) as well as live cell imaging techniques.