Figure 1.

Mathematical model of mutual inactivation shows production rate-dependent role of DLL3

(A) Schematic of Notch, DLL1, and DLL3 interactions in lateral inhibition with mutual inactivation (LIMI).

(B) Schematic of HES1^GFP-positive cells from an RPR2;Hes1^GFP tumor serving as a reporter cell line, with GFP expression from the Hes1 locus to monitor the effect of ectopic DLL3 expression in regulating Notch activity.

(C) Flow cytometry of HES1^GFP-positive cells with (blue) and without (black) ectopic expression of DLL3 (representative of n = 4 biological replicates).

(D) Percentage of GFP^high HES1^GFP-positive cells with and without ectopic expression of DLL3. Unpaired t-test, data represented as mean ± s.d. ∗∗∗p<0.001.

(E) Log(H_max/H_min) at steady state were calculated as a function of β_D3 and β_D. Regions with values greater than 0 (light blue to yellow regions) support patterning, whereas those with 0 (dark blue) do not.

(F) Hexagonal cell lattice with LIMI showing that DLL3 expression can lead to sparser patterns of HES1^high cells (blue) or no pattern (homogeneous color).

(G) H_max as a function of β_D3 and β_D.

(H) H_min as a function of β_D3 and β_D.

(I) Simulations with the indicated parameters for β_D3 showing H levels in cells with high and low final H levels.

Green, red, purple, and gray dots in (E), (G), and (H) correspond to the parameters used in (I). See also Figure S1 and Table S1.