“…This gene is activated immediately upon the birth of the fourth cleavage micromeres in response to two maternal transcriptional inputs at this stage confined to these cells (2,3). Perturbation experiments showed that these are Otx, a transcription factor nuclearized in the fourth cleavage micromeres, but later in other cells as well (4), and maternal -catenin, which is nuclearized downstream of a maternal anisotropy in activated Dishevelled protein, tethered at the vegetal pole of the egg (5, 6). As described earlier (1,7,8), pmar1 transcription activates a double-negative logic gate, which accounts for the institution of the whole downstream skeletogenic regulatory state, formulated by transcription of a specific set of regulatory and signaling genes.…”