Standfirst
A new study identifies bipotent neuromesodermal progenitors as key players in embryonic differentiation.
PHOTOALTO
Gastrulation is a key process during early embryonic patterning in which a single epithelial layer develops into three germ layers — ectoderm, mesoderm and endoderm — and the axes of the embryo are formed. A recent study challenges the paradigm that the three germ layers are the primary intermediates in the differentiation of pluripotent epithelium into tissue-specific precursors and identifies bipotent neuromesodermal progenitors that have a crucial role in axial elongation and differentiation.
To track early development in mouse embryos, Tzouanacou and colleagues used a single-cell labelling method that relies on the spontaneous reversion of an inactive lacZ gene (laacZ) carrying a sequence duplication to an active lacZ reporter through a rare recombination event. Clones derived from laacZ/lacZ-revertant progenitor cells were followed to see which tissues of the embryo they contributed to, and the size of the clones allowed the authors to estimate the time at which the progenitor cells were labelled.
The tissue distribution and size of over 1,000 clones detected in embryonic day (E)8.5 (early organogenesis stage) embryos revealed that the endoderm and surface ectoderm segregated from other lineages before the end of gastrulation but, intriguingly, a large proportion of the neuroectoderm clones also showed labelling in the mesoderm, which suggests that common neuromesodermal progenitors persist at least into late gastrulation.
Next, the authors examined E10.5 embryos and found that common neuromesodermal progenitors persisted at the tail-bud stage. Based on the distribution of the clones, they suggested that the neuromesodermal progenitors could differentiate to colonize more posterior regions of the elongating anterior–posterior axis while still maintaining cells in the progenitor region, indicating that these cells have the capacity for self renewal. The authors also suggest that the composition of the neuromesodermal progenitor pool evolves during axis elongation, so that as early progenitor pool descendants are partly depleted, there is an expansion of a progenitor subpopulation that mainly contributes to the posterior axis.
The identification of neuromesodermal progenitors in this study may have important implications for strategies aimed at differentiating embryonic stem cells towards particular tissue lineages in vitro, as well as for understanding the developmental phenotypes of mouse mutants.