From Cat To Mouse

We primarily use the mouse model system to gain insights into how X-inactivation occurs. In the mouse, there are two forms of X-inactivation: imprinted and random.

In imprinted X-inactivation, the paternal X-chromosome is inactivated. This form of X-inactivation occurs in all cells of the pre-implantation mouse embryo. Imprinted X-inactivation is then maintained in the two cell types that will give rise strictly to extra-embryonic tissues - the trophectoderm and the primitive endoderm. The trophectoderm ultimately contributes to the placenta and the primitive endoderm to the yolk sac.

The epiblast cells that are destined to give rise to the embryo itself (shown in green), on the other hand, reactivate the paternal-X prior to undergoing random inactivation of either the paternal- or the maternal X-chromosome in individual cells. The silencing of the inactive-X, therefore, can both be long lasting as well as reversible - a hallmark of epigenetic transcriptional regulation.

In addition to the mouse, ongoing and future projects in the lab entail examining X-inactivation processes in human embryonic stem cells and in rat embryos and stem cells as well as a comparative analysis of X-inactivation patterns across placental and marsupial mammals. Through these approaches, we seek to elucidate evolutionarily conserved principles of X-chromosome dosage compensation amongst and between eutherian (placental) and metatherian (marsupial) mammals.