University of Edinburgh scientists working with colleagues in the United States have shed light on a critical stage of cell fate differentiation, a discovery which will influence fundamental cell biology and potentially aid our understanding of stem cell biology.
A BBSRC-funded mathematical modelling team at the University of Edinburgh together with an experimental team at the University of Pennsylvania demonstrated that a structure called a septin ring was crucial in the process of cell division and differentiation in budding yeast.
When budding yeast cells divide in a process called asymmetric cell division the original 'mother' cell and the newly formed 'daughter' cell are non-identical, follow distinct developmental programmes and even age differently.
The single-cell budding yeast is therefore an excellent model organism to study asymmetric cell division and cell fate differentiation since during each cell division a daughter cell is born with a replicative age reset to zero, like a typical stem cell, while the mother cell continues to age.
The teams discovered that the formation of the septin ring at what will become a membrane boundary between mother and daughter cells differentiates them from each other long before cell division is complete.
This process is heavily dependent on a molecule called Cdc42, which promotes the formation of the septin ring, and then concentrates in the daughter cell, causing its differentiation from the mother cell.
The team demonstrated for the first time that the hollowing of septins recruited by Cdc42 into the shape of a ring is caused by a highly localised insertion of new membrane vesicles, the process known as polarized 'exocytosis'.
Dr Andrew Goryachev, Reader in Computational Cell Biology at the University of Edinburgh, said: "This project shows how a close collaboration between theory and experiment can result in a breakthrough study that not only presents new and unexpected experimental findings, but with the heavy use of cutting-edge mathematical modelling answers a number of long-standing questions that have sparked much controversy and discussion in the international scientific literature."
Septins are already known to play important roles in diverse cellular functions and human diseases, including cell growth, division, cell migration, bacterial infection, cancer, and neurodegenerative diseases and this study pushes forward our understanding of the mechanisms of septin ring biogenesis.
Notes to editors
Okada et al., Daughter Cell Identity Emerges from the Interplay of Cdc42, Septins, and Exocytosis is available to view at http://dx.doi.org/10.1016/j.devcel.2013.06.015