16 TGF-β Family Signaling in Early Postimplantation Development of the Mouse

Upon implantation at embryonic day 4.5 (E4.5), the mouse embryo, a blastocyst, initiates the formation of the egg cylinder. During this process, the inner cell mass, located at the embryonic side of the blastocyst, differentiates into the epiblast and the visceral endoderm. On the opposite (abembryonic) side of the blastocyst, the mural trophoectoderm differentiates into the extraembryonic ectoderm, forming a radially symmetric structure by E5.5 (Fig. 1a,b). The future fetus is derived entirely from the epiblast. The visceral endoderm and extraembryonic ectoderm will contribute only to extraembryonic structures such as the future placenta. At the time of implantation, the early embryo is most clearly defined by this embryonic–abembryonic axis. The first sign of overt morphological asymmetry in the embryo begins with the formation of the anterior visceral endoderm, an extraembryonic tissue, at E5.5. The anterior visceral endoderm first appears at the distal tip of the egg cylinder and is defined by molecular markers such as expression of Hex . This distal region of the visceral endoderm starts to move toward the future anterior side at E5.5, and by E5.75–6.0, the distal visceral endodermal cells are located at the future anterior side of the embryo to form the anterior visceral endoderm (Rivera-Perez et al. 2003; Srinivas et al. 2004). Although the formation and anterior movement of the anterior visceral endoderm have long been thought to mark the initiation of anterior–posterior axis formation, recent findings have identified molecular asymmetries along the prospective anterior–posterior axis before the movement of the...