Control circuits for determination and transdetermination: interpreting positional information in a binary epigenetic code.

Positional information in an embryo requires interpretation to guide spatially ordered differentiation. Evidence, from dtermination and transdetermination among imaginal disc derivatives in Drosophila, suggests the interpretative commitment, or determination, is carried by entities possissing only two alternate states each. This hypothesis correctly predicts pairs of classes of mutants affecting complementary subsets of imaginal discs. Four such complementary pairs define four boundaries separating the various imaginal discs on the fate map of the egg. Crossing any boundary corresponds to a change in state of the associated determination circuit. Using these boundaries, the model makes 43 predictions about relative transdetermination frequencies. Thirty-four appear correct. This has an a priori probability of less than 10- minus 4. False predictions appear to reflect incompleteness in the theory. The four boundaries on the fate map presumably correspond to threshold levels of spatial gradients constituting positional information; on one side of a threshold one circuit state occurs, on the other, the second state. The last four cleavage divisions in Drosophila melanogaster occur as four mitotic waves with geometries similar to the four boundaries. Disc determination happens at about this time. These waves may be, or reflect, the signalling system carrying positional information. Focus on the interpretive machinery, the determination circuits, suggests two slightly new concepts: (1 the set of possible combinations of states of determination circuits constitutes an epigenetic code, thus raising familiar coding questions concerning redundancy or nonsense words; (2) each circuit may respond to its own gradient or positional signal distributed in two or three dimensions.