Morphogens, Embryonic Patterning and Axis Formation

The overall body plan of organisms can be defined by three major axes that are patterned during embryogenesis: the anteroposterior (A-P), dorsoventral (D-V), and left-right (L-R) axes. During Drosophila development, embryonic pattern is established by transcription factors that diffuse through the early syncytium to form morphogenetic gradients. In mammals, embryonic pattern formation was previously thought to be established during the process of gastrulation. More recently, similarities among mammalian blastocysts and Xenopus oocytes suggest that polarity exists earlier in development prior to the onset of gastrulation. This is evidenced by asymmetric gene expression patterns that correspond to the developing A-P axis, which is considered the first break in embryonic symmetry. Axis formation is regulated by signaling molecules such as members of the BMP, Wnt, transforming growth factor-beta (TGF-beta) and fibroblast growth factor (FGF) families. In addition, secreted agonists and antagonists that function in a biological reaction-diffusion system are thought to maintain morphogen gradients across cell fields. For example, during L-R patterning, Nodal induces its own expression and that of Lefty, a Nodal feedback inhibitor with a longer diffusion range. These feedback mechanisms, local activation and long-range inhibition, allow cells near the Nodal growth factor source to receive high levels of signal while a consistent gradient ensures that distant cells experience little to no Nodal signaling.