Figure 7.

Model of cyp26b1, cyp26c1, and hoxb1 in Cell Identity Switching

(A) Segmental regulation of low cyp26b1 and cyp26c1 expression in r3 (magenta) and high expression in r4 (green) maintains high [RA] in r3 and low [RA] in r4.

(B) In r3, egr2 represses cyp26b1 and cyp26c1 expression, which in turn keeps RA levels high, repressing hoxb1 expression. Egr2 also directly autoregulates its own expression and represses hoxb1 expression. In r4, high cyp26b1 and cyp26c1 expression maintains a low level of RA, permitting expression of hoxb1. Hoxb1 autoregulates its own expression and represses expression of egr2.

(C and E) When an r3 cell intermingles into r4, the surrounding cells have high cyp26b1 and cyp26c1 expression, which reduces the level of RA within the ectopic r3 cell. This promotes upregulation of hoxb1 in the ectopic r3 cell, which represses egr2 expression, causing the r3 cell to change identity to r4.

(D and F) When an r3 cell intermingles into r4, but cyp26b1 and cyp26c1 are knocked down, the surrounding r4 cells no longer have high cyp26b1/c1 expression, so RA levels remain high in the ectopic r3 cell. Consequently, egr2 is not downregulated in the ectopic r3 cell (F).