Figure 1.
Early mouse development and the role of Wnt3 in mammalian gastrulation. (A) Preimplantation blastocyst stage mouse embryo. (B) After implantation, the inner cell mass (ICM) expands into a radially symmetric cup of epithelium known as the epiblast that gives rise to the entire embryo proper. The polar trophectoderm, initially overlying the ICM, gives rise to the ectoplacental cone and the extraembryonic ectoderm (ExE) that do not contribute to the embryo proper, but form the placenta and trophoblast giant cells to support embryonic development. The ExE and epiblast is also covered by a layer of visceral endoderm (VE) derived from the primitive endoerm in the blastocyst. (C) Between E5.5 and 6.0, the distal VE undergo proximally oriented unidirectional movement, leading to the formation of the anterior VE (AVE) that marks the future anterior side of the embryo. The AVE inhibits Nodal signaling anteriorly to restrict Nodal-induced primitive streak formation in the posterior epiblast adjacent to the ExE. (D) During gastrulation, epiblast cells ingress through the primitive streak to give rise to the mesoderm and definitive endoderm. (E) Wnt3-induced canonical Wnt signaling is an integral part of a global signaling network that regulates gastrulation. Epiblast-derived Nodal activates the expression of Bmp4 in the neighboring ExE. Bmp4 signals back to activate Wnt3 expression in the epiblast. In turn, Wnt3 potentiates Nodal signaling by promoting the expression of Nodal and its coreceptor Cripto (important for Nodal auto-induction), thereby establishing the Nodal-Bmp4-Wnt3 positive feedback loop to sustain gastrulation. In addition, Wnt3 is also required for Fgf8 expression, which promotes ingressing epiblast cells to migrate out of the primitive streak during gastrulation.