Dr Berenika Plusa - research
In our lab we investigate various aspects of regulative abilities of early mammalian embryos using the mouse as a model organism. In particular we are focused on understanding how the first cell fate decisions are made during preimplantation mammalian development and what is the role of cell-cell communication and cell plasticity in this process.
At the present we concentrate on identifying the point during development when cells become irreversibly committed to the first three embryonic lineages and factors that contribute to this decisions.
According to the current model of lineage segregation in the early embryo, cells are already determined to give rise to only one lineage (PrE or EPI) prior to visible morphological evidence of PrE formation on the surface of the ICM which reflects cell sorting into and lineage segregation. Our experiments aimed to test this model. Using transgenic mice expressing histone-GPF under regulation of the Pdgfra promoter, an early marker of PrE, we follow the fate of presumptive PrE and EPI cells in the chimaera assay. We observe that at blastocyst stage, even after PrE and EPI linages can be clearly distinguished in the ICM, cells are not fully committed to contribute exclusively to one lineage, although the process of specification has already begun. Progeny of isolated presumptive EPI and presumptive PrE (pre-PrE and pre-EPI cells) cells can individually contribute to more than one lineage. Furthermore, these cells are able to re-program and contribute to the lineage different than the pre-specified one. However, pre-PrE and pre-EPI cells show different potential to reprogram. While pre-PrE cells can contribute to all three embryonic lineages with equal ability, pre-EPI cells show very limited ability to contribute to PrE lineage. These data support the notion that cell determination is a gradual process that becomes irreversible only at later stages of development and the populations of presumptive PrE and EPI cells may be in different stages of the commitment process.
Our previous work suggest that the segregation of first lineages is driven by additional regulatory events, including sensing of positional information that results in up- and down-regulation of key transcription factors. This, together with differences in cell adhesion, contributes to the formation of the first three embryonic lineages.
In our current work we observe that interfering with positional information provided by cell polarity results in changes in expression and localisation of lineage-specific transcription factors. This finding is consistent with our model and points to cell polarity as a key player during early lineage specification.