Robustness gains require Crabp-mediated RA degradation. (A,B) E value distributions for models with either a 5-fold increase (A) or decrease (B) of RA synthesis rate with respect to 10- (green), 5- (magenta), or 2-fold (red) increases in Vbp. (C) Percentages (x-axis) of wild-type (blue bars), mild (red bars), moderate (green bars) and severe (black bars) phenotypes resulting from injection of different amounts of Crabp2a mRNA per embryo (y-axis) treated with 5 nM RA. (D,E) Simulations of 5-fold increases in RA synthesis rate in which binding proteins: (1) have all three mechanisms; (2) do not transport RA to receptors (jB=0); (3) do not sequester RA (jA=0); (4) do not transport RA to Cyp26 degradation (rabpdeg=0); (5) must bind RA to allow degradation (radeg=0); and (6) are absent.