Mammalian development can be viewed as a series of restrictions in cell potency. As the embryo undergoes cleavage, implantation and gastrulation, cell potency is gradually restricted (with the exception of the germline) until cells commit to a particular pathway of differentiation. This process depends on the generation of heritable epigenetic states that must be perpetuated as the embryo progresses in development. How are these epigenetic states established and maintained? In this issue of the Journal of Cellular Physiology, four articles summarize recent advances in our understanding of signaling events, cell movements and epigenetic mechanisms that control cell fate and shape the early mouse embryo.
X-inactivation is a prime example of an epigenetic phenomenon that regulates early mammalian development. Twenty years ago, the realization that Xist was responsible for silencing the X-chromosome (Brown et al., 1991), opened the door to fascinating epigenetic discoveries. Today, Xinactivation research continues to generate captivating and provocative results. As highlighted in the article by S. Kalantry, recent studies, suggest that there can be X-chromosome inactivation in the absence of Xist. In addition, RNF12 has been proposed to be at the core of the long sought counting mechanism by which a cell senses the number of Xchromosomes that it harbors.
The article by Trask and Mager examines the role of chromatin remodeling complexes in the establishment and maintenance of embryonic epigenetic marks. Interestingly, this field of research was greatly aided by the positional cloning of Eed (Schumacher et al., 1996), a lethal mutation that affects gastrulation and whose gene codes for a member of the polycomb repressive complex 2 (PRC2). Eed mutants have been instrumental in studies that linked PRC2 to the maintenance of chromatin modifications leading to imprinted and random X-inactivation. Since then a plethora of members of the PRC2 and other chromatin remodeling complexes have been identified in mice and the search continues for the identification of polycomb responsive elements in the genome.
Sunmonu and co-workers explore the role of Fgf8, a gene required for cell movements during gastrulation that, like Eed, is essential for embryo survival (Sun et al., 1999). Fgf8 has multiple