How do cell division and cell fate transition crosstalk?
During development, while cells progressively lose their developmental potential and gain specialized function, they also divide to build a multicellular organism. Cell division is believed to be a punctual event, leading to the separation of two distinct daughter cells. However, many multicellular organisms, at one point of their development, maintain cytoplasmic bridges connecting the two daughter cells for a long period instead of severing the connection in the process called abscission. Modulation of the rate of abscission is indeed present in all the animal kingdom as well as in their closest unicellular relative, choanoflagellates. In particular, all animals possess bridges in the germ cell lineage, where they are thought to allow exchange and participate in nutrition, similar to bridges linking individuals in choanoflagellate colonies. However, in multicellular animals, cytoplasmic bridges are present in other tissues and during other developmental stages. In particular, bridges are present in cells of high developmental potential for example early embryos (mouse, mollusk, cnidarian and tunicates), adult pluripotent stem cells (for example in cnidarian), or, as I discovered during my postdoc, mouse embryonic stem cells. Yet nothing is known about the mechanisms controlling speed of abscission, how bridges influence cellular decision making during multicellular development, and how abscission can be quickly rewired when fate transitions are triggered.
My research projects aims at:
- Exploring whether a slow rate of abscission is a feature of high developmental potential by systematically measuring duration of abscission in embryos, pluripotent and multipotent adult stem cells and tissues, and investigating the conservation of the molecular mechanisms underlying slow abscission.
- Understanding how abscission mechanisms can be quickly rewired when fate transitions are triggered, in particular how cells can sever daughter cell connection upon differentiation.
- Understanding how abscission regulates developmental progression and how we can find new approaches to engineer developmental potential by targeting the division machinery.
Methods (past and future)
- Mouse Embryonic Stem Cells/mouse embryo/iPSCs/other animal embryos, tissues and organoids
- Live confocal microscopy/electron microscopy/light sheet microscopy
- Comparative developmental biology
- Dr Thibaut Brunet (UC Berkeley)
- Prof Kevin Chalut, Dr Céline Labouesse (Stem Cell Institute, Cambridge, UK)
- Prof Jonathan Chubb (MRC LMCB, University College London, UK)
- Dr Gautam Dey (EMBL, Germany)
- Dr Edouard Hannezo (IST Austria)
- Prof Ewa Paluch (PDN, University of Cambridge)
- Dr Marta Shahbazi (MRC, LMB, Cambridge, UK)
- Dr Ian White (MRC LMCB, University College London, UK)