Specification, maintenance and elimination of stem cell progenitors for the mammalian anteroposterior axis

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During embryo development, the spinal cord, vertebral column and muscles are laid down by stem cells. We have shown that these stem cells are unique for several reasons. Unlike embryonic stem (ES) cells, which can make any tissue in the body, or neural stem cells, which only make nervous tissue, these 'neuromesodermal' or 'NM' progenitors make two very distinct embryonic tissue types, the neural tube (which then generates spinal cord) and the mesoderm (which makes muscle, bone and cartilage). These stem cells are born very early during development and are active until the precursors of spinal cord and vertebral column are laid down. They then are completely removed from the embryo. These cells would be a useful source of differentiated muscle, bone, and spinal cord if we could grow them in a culture dish. In fact, unlike ES cells, NM progenitors do not make malignant tumours when injected in adult mice. Recently, we have generated, in cell culture, NM progenitor-like cells and we plan to study how these cells are generated, how they make neural tube and mesodermal cell types, and how the embryo knows when to eliminate them. Several human birth abnormalities including caudal regression syndrome, a high risk for diabetic mothers, may arise because NM progenitors are not correctly eliminated, and we will use our knowledge of NM progenitors in the embryo to study whether this is the case. This programme therefore combines study of cells in embryos with cells in culture to understand development and disease, and to produce cell types that may be useful in the future for cell therapies.