Fig. 1: Nonlinear cis-inhibition establishes the twin peaks of Notch activity.

a Optic lobe in a lateral view showing the twin peaks of Notch activity (NRE-dVenus, green), wavefront (Lsc, blue), and Dl (magenta) in the left panel. The proneural wave progresses in a medial-to-lateral orientation (left to right). Asterisk indicates the second peak of N activity in NBs. Orange arrow indicates the gap between the twin peaks. The right panel shows that Lsc expression at the wavefront triggers the differentiation from NE to NB and overlaps with Dl expression and the first peak of N activity. b A section showing the twin peaks of Notch activity (mγGFP, green), wavefront (Lsc, blue), and Dl (magenta). White arrows show Dl expression at the wavefront. Orange arrow indicates the gap between the twin peaks of N activity. Schematic shows that NBs sequentially express temporal transcription factors, Hth (orange), Klu (magenta), and Ey (blue), which control the production of neurons expressing Hth/Bsh, Run, and Drf, respectively. c, d N activity is visualized by NRE-dVenus (c) and mγGFP (d) in green and compared with the distributions of Dl (magenta) and Lsc (blue). Signals in the dotted box areas are plotted in the right panels. Arrows indicate the twin peaks of N activity. Scale bars indicate 20 μm (a–d). e–g Results of numerical simulations: left panels show the two-dimensional patterns of N and D. Middle panels show the one-dimensional patterns of N (green), D (magenta), E (black), and A (blue; y = 13). The values of N, D, and E are 30, 10, and 10 times multiplied, respectively. Right panels in (f, g) compare the profiles of trans-activation (black) and cis-inhibition (red) in response to D. The values of trans-activation are four times multiplied because one cell could receive trans-activation from as many as four adjacent cells. e Single peak of N activity in the previous mathematical model in which the effect of cis-inhibition is linear. f, g Twin peaks of N activity are reproduced by introducing step function (f) or Hill function (g) to cis-inhibition.