A microtubule organizing center in the early mouse embryo

Microtubules, the largest filaments of the internal skeleton of a cell, are typically emanating from a central structure inside a cell, the centrosome. However, the cells of the early mammalian embryo are lacking centrosomes. Therefore, it has remained unknown how the microtubule cytoskeleton is organized during the first stages of development. Here, we discovered how mammalian cells organize their internal skeleton during the earliest stages of embryonic life.

HFSP Long-Term Fellow Jennifer Zenker and colleagues
authored on Thu, 31 August 2017

Every cell in our body has an internal skeleton made of hundreds of filaments called microtubules. Deregulation of this microtubule ‘cytoskeleton’ can cause infertility, cancer and neurodegeneration. Microtubules typically grow from a region of the cell called the centrosome, which acts as a microtubule organizing center.

Figure: Visualisation of the internal cytoskeleton of the cells of the early mammalian embryo.

Scientists at the Institute of Molecular and Cell Biology of A*STAR in Singapore have now discovered a microtubule organizing center, which acts like a centrosome in the early embryo. Using laser imaging technologies in live mouse embryos (which develop similarly to humans during early embryonic stages), the scientists visualized a region inside the cells from where microtubules emanate. They demonstrated that physically ablating this structure with nanolasers, or deleting genes required to form this structure, resulted in embryos with disorganized microtubule networks that were unable to develop normally. Moreover, the scientists found that the microtubules organized by this new organizing center are critical to transport proteins between distant cellular compartments, like the cell nucleus and the outer cell membrane.

Together, this work opens new ways to understand how microtubules are organized inside the cells of our body, and to design new strategies to treat diseases linked to abnormalities in the cell cytoskeleton. It advances our understanding of how a healthy embryo forms during the preimplantation stages of development and will provide new ways to monitor normal versus abnormal development of human embryos cultured in vitro and used for assisted reproduction (ie, IVF) and preimplantation genetic diagnosis (PGD).

Reference

A microtubule-organizing center directing intracellular transport in the early mouse embryo. J. Zenker, M. D. White, R. M. Templin, R. G. Parton, O. Thorn-Seshold, S. Bissiere, N. Plachta. Science  01 Sep 2017:Vol. 357, Issue 6354, pp. 925-928; DOI: 10.1126/science.aam9335

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