Dresden 2011 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 5: Tissue Dynamics \& Developmental Processes

BP 5.7: Vortrag

Montag, 14. März 2011, 16:00–16:15, ZEU 250

Oct4 kinetics predicts cell lineage patterning in the early mammalian embryo — Nicolas Plachta¹, •Tobias Bollenbach^2,3, Shirley Pease¹, Scott E. Fraser¹, and Periklis Pantazis¹ — ¹California Institute of Technology, Pasadena, CA, USA — ²Harvard Medical School, Boston, MA, USA — ³IST Austria, Klosterneuburg, Austria

Transcription factors (TFs) are central to sustaining pluripotency in mammalian development. Here, we establish a fluorescence decay after photoactivation (FDAP) assay to quantitatively study the nuclear transport kinetics of Oct4, a key TF controlling pre-implantation development in the mouse embryo. Combining FDAP measurements with a physical description of nuclear transport, we reveal that each cell in a developing mouse embryo exhibits one of two distinct Oct4 kinetic profiles, before there are any morphologically distinguishable differences or outwards signs of lineage patterning. By tracing the lineages of the cells in these two distinct sub-populations, we find that Oct4 kinetics predicts lineages of the early embryo. Cells in which FDAP reveals slower Oct4 kinetics are much more likely to contribute to the pluripotent cell lineage which creates the inner cell mass and later gives rise to the fetus. In contrast, cells with faster Oct4 kinetics contribute almost exclusively to the extra-embryonic lineages which later form the placenta. Our findings identify Oct4 nuclear transport kinetics, rather than differences in total expression levels, as a predictive measure of cell lineage patterning in the early mouse embryo.

Reference: N. Plachta et al., Nature Cell Biology, accepted.