Genome Remodelling
The knowledge of the molecular mechanisms involved in cell differentiation during embryonic development is central for the understanding of differentiative processes including those involved in the progression of genetic diseases. This knowledge would permit the development of new strategies for cell and gene therapies. It has recently been shown that mice can develop to term from enucleated oocytes injected with the nuclei of somatic cells. These experiments demonstrate the capacity of the mouse oocyte to remodel the genetic programme of a somatic cell nucleus in order to make it capable of initiating and continuing embryonic development (Wakayama et al., 1998). The activation of zygotic genes occurs in the mouse by the 2-cell stage and it is a crucial event in the life of the newly formed mouse embryo as lack or wrong timing of zygotic gene expression leads to the death of the embryo. For these reasons the genetic modifications (reprogramming) induced by the oocyte over the newly injected somatic nucleus must be completed before zygotic genome activation occurs. The understanding of the mechanisms that intervene in the processes of cell differentiation and in those that make it a reversible process, would allow to repeat the process of nucleus reprogramming in an in vitro system, without the use of the female gamete.

At LBS we are studying the genome modifications that might be involved in the reprogramming process following the transfer of a terminally differentiated somatic nucleus into the cytoplasm of an enucleated oocyte (Nuclear Transfer, NT).

We are tacklying these studies through two main lines of research:

1) Analysis of the timing and quantitation of early embryonic genes in preimplantation embryos obtain by IVF and NT;

2) Remodelling of nuclear and cell functions by culture in cell extracts.