Mutual Inactivation of Notch Receptors and Ligands Facilitates Developmental Patterning
(A) Schematic of vein boundary formation. During vein formation a gradient in DSL production from the center of the vein (left, red) is converted into two sharply defined sidebands of Notch target expression (right, green). (B) Cartoon of the Bandpass regulatory mechanism, in which the boundary is determined by a transcription-level filter which determines the mapping from Notch activity to cell fate. Note that there is no feedback on the signaling system. (C) Cartoon of the Mutual Inactivation model regulatory mechanism, in which the level of Notch signaling directly determines the cell fate. Note again that there is no feedback on the signaling system. (D) Simulations of boundary formation. Top: DSL gradient profiles (three red curves) with varying slopes, chosen to generate side bands at a fixed position. Middle, bottom: Profiles of target reporter concentrations for the three slopes shown in the top panel for the MI model (middle) and the BP model (bottom). (E) Dependence of peak width on slope for the two models. In the MI model (top panel), peak width, w, remains small over a range of gradient slopes and strengths of the mutual inactivation interaction, . Here, smaller corresponds to stronger cis-inhibition (See Eqns. 1–2). In the BP model (bottom panel) peak width depends on the gradient slope as well as on the bandpass steepness parameter, . Here, higher corresponds to a steeper bandpass (see Eqn. 6 and Fig. S1). Note that for the BP model, DSL production profiles were shifted to lower levels (see Table S1) but maintained the same slopes compared to the profiles shown in (B, top). This made sure that the bandpass is in a functional regime in which Notch signaling varies linearly with position (e.g. as in Fig. S1B). See Table S1 for parameter values.