The transformation of a mammalian embryo from a tiny soccer ball-like structure into a newborn with four limbs, a beating heart and big bright eyes is one of the most remarkable and fundamental processes of life. Inside the soccer ball-like embryo resides a handful of “all-rounder” cells, known as pluripotent cells, which can give rise to any type of cell in the adult body.
Until recently the inimitable potency of pluripotent cells has been known to be regulated by a combination of genetic, epigenetic and external factors. We were the first to discover that pluripotent cells develop and mature into distinct cell types also based on the functions of their inner scaffolding, the microtubule cytoskeleton, which was until then widely regarded as disorganised and its contribution to cell fate specification was largely ignored.
Inside a cell, organelles and proteins are usually not randomly distributed but are assigned to regions where they are needed. The cell utilises the microtubule cytoskeleton as the road map to localise organelles and to trigger the relay of signals intra- and intercellularly. By performing innovative live imaging of preimplantation mouse embryos, we discovered an unprecedented form of non-centrosomal microtubule organisation required for the formation and maintenance of pluripotency. Dependent on the microtubule anchor and nucleator Calmodulin-Spectrin associated protein 3 (CAMSAP3), this form of non-centrosomal microtubule organisation orchestrates the asymmetric distribution of cell adhesion proteins, RNAs and organelles which results in an unequal inheritance of information, and differential cell fate decisions of daughter cells.
Our discoveries comprehensively address the cell biological hallmarks of pluripotency during mammalian embryogenesis, orchestrated by the microtubule cytoskeleton. By addressing this knowledge gap, we can harness our discoveries to develop novel therapeutics for regenerative medicine and fertility.