Figure 1.

A schematic of embryonic upper limb development

An illustrative drawing describes a human embryo at Carnegie stage 12 (top left; approximately 4 weeks after conception), when the limb bud forms as a ventrolateral bulge and begins to emerge outwardly. Also shown is a magnified illustration depicting the 3D patterning of the upper limb bud and a dissected view of the anatomical position between ectoderm and mesoderm. The P/D, A/P, and D/V axes are labeled with different colors. The AER is labeled at the brown epithelial region, ZPA is shown as a gradient-based yellow zone. Bottom right: illustration of a mutual genetic antagonism between the short isoform of GLI3 (GLI3R) and HAND2 that is required to establish a “pre-patterning” of the A/P axis prior to formation of the SHH-ZPA gradient. Top right: P/D elongation is regulated by many signaling elements, including FGF8, TP63, and BHLHA9.