The spatial and temporal configuration of the microtubule cytoskeleton is pivotal for tissue integrity and function. Whereas in proliferating, undifferentiated somatic cells, the centrosome serves as the major microtubule organizing center (MTOC), most differentiated cells, for instance epithelial cells, neurons and muscles, adopt a polarized non-centrosomal microtubule architecture. However, the regulation of microtubule growth and dynamics during the formation of the inner pluripotent cell mass of the early mammalian embryo lacking centrosomes remained elusive.
Using live imaging, I discovered a new form of non-centrosomal microtubule organization creating a shared asymmetric microtubule network between every pair of sister cell across the preimplantation embryo. Contrary to centrosome-containing cells, the cytokinetic bridge does not undergo stereotypical abscission after cell division in the mouse embryo. Instead, it transforms into a non-centrosomal MTOC by accumulating the microtubule minus-end protein CAMSAP3 and promoting microtubule nucleation. I show that the microtubules emanating from this MTOC direct the intracellular transport of membrane polarity proteins such as E-cadherin which is required for the formation of the pluripotent inner cell mass. Moreover, in line with the absence of centrosomes, the mitotic spindles of the early embryo are anastral. However, a distinct polar microtubule network establishes at the end of cell division causing the exclusion of F-actin from the apical cortex of all outer cells of the embryo. The resulting apical actin rings expand towards cell-cell junctions, zipper and seal the embryo to allow the formation of the blastocyst.
Together, live imaging reveals a novel mechanism how non-centrosomal microtubules are organized and function during early mammalian embryogenesis.