CRM scientists have identified a new role for the gene regulator Otx2 at a very early stage in development of primordial germ cells (PGCs), the cells that lead to all germ cells.
Professor Ian Chambers and colleagues looked at the first stages of germ cell formation focussing on the molecule BMP4 and found that it blocks the activity of Otx2, a transcription factor that directs the development of non-germ cells, known as somatic cells.
The team showed that reduction in Otx2 activity at a specific stage in development is crucial to the development of germ cells.
Early in development cells reach a “decision point” where they either differentiate to form germ cells or somatic cells. Germ cell differentiation is dependent on BMP4 activity and gene regulators known as PGC transcription factors.
The study looked at lab grown cells in which the gene for Otx2 was deleted. This showed that at this key decision point, those cells were more likely to become primordial germ cells. Similarly deletion of Otx2 in mouse embryos led to an increase in primordial germ cell numbers.
The team went on to show that in the absence of Otx2 activity PGCs formed independently of the otherwise essential BMP4 signal, with germline entry initiating even in the absence of the PGC transcription factor Blimp1.
This study is published in Nature and was funded by the Medical Research Council (MRC) and the Biotechnological and Biological Sciences Research Council.
Professor Ian Chambers from the University of Edinburgh’s MRC Centre for Regenerative Medicine, who led the study, said:
In the past studies of germ cell identity have focused on activity much later down the chain of events. Now we can begin to see much earlier events occurring as cells commit to germ cell development. These exciting findings open the door to further work which will allow us to better understand the molecular interactions that control the earliest steps cells use to change identity in general and specifically how germ cells separate from all other cells.