|Select image to enlarge|
Alternative explanations for why cells cannot normally leave the compartment where they are born. Part of the A/P interface is shown in each panel, and cell types are enlarged at right.
According to the Selector Affinity Model (above) [904, 1369, 2441, 2928] the ON or OFF state of a cell's engrailed (en) gene 'selects' whether it adopts P- or A-type identity. A-type cells use one kind of homophilic adhesion protein (round hook), P-type cells use another (zigzag hook), and A-P binding is disfavored. Only when cells switch identities -- e.g., the depicted enGOF A clone (shaded) -- can they cross the A/P line (gray bar). In this schematic, one of the clone's cells has already crossed.
The Border Guard Model [364, 1839, 3627] postulates a unique adhesion protein (square hook) for A (en-OFF) cells within a certain range (~5-10 cells vs. the 2 cells shown here; cf. Fig. 6.3) of the A/P line. These border ('B') cells turn ON decapentaplegic (dpp) in response to Hedgehog (Hh) diffusing from the P region, and they join into chains . No P or A cell can enter the B zone unless it turns ON dpp. A-type cells can do so when they approach the A/P boundary, but P cells cannot since en inhibits dpp. Hence, the B/P line restricts cell lineage, while the A/B line does not. If a B clone (shaded) stops transducing Hh due to smonull (smoothenednull), then it forfeits its B identity but not its en-OFF state and so becomes A-type. The B zone then shifts anteriorly because (1) smonull suppresses the Hh receptor Ptc (Patched), and (2) Hh diffuses farther over cells having less Ptc [754, 755].
Interestingly, homotypic mingling (which both models presume) occurs when fast-growing clones cross from one foreleg disc to the other (A-to-A or P-to-P) after they fuse (not shown) . Segregation of cell types might not use different linkers (as depicted here) but could instead rely on different linker densities [4070-4074]. Indeed, studies of ptcGOF clones suggest that A and P affinities differ quantitatively since these partly deaf clones behave as if they have an intermediate affinity . Other molecules (not shown) could maintain epithelial integrity by non-specific (or extracellular matrix) binding [1957, 3937]. Adapted from .