Fig. 5.3. NOTCH signaling and cell morphology.

(A) Contact area and membrane diffusion affect signal strength. Schematic representation of a two-cell reaction-diffusion model that takes into account contact area and membrane dynamics. The model identified two distinct regimes depending on the ratio between the contact area, A, and the area defined by the diffusion length scale, λ². The diffusion length scale is defined by $\lambda =\sqrt{D/k_{endo}},$ where D and k_endo correspond to the diffusion coefficient and endocytosis rate of DELTA, respectively. While in one regime (λ² < A), signaling depends on the contact area, in the second regime (λ² > A), signaling is independent of the contact area. (B) Contact area dependent signaling can bias cell fate. Left - A schematic representation of a lateral inhibition model that takes into account the dependence of signaling on contact area. The model assumes that NOTCH signaling in each cell depends on the number of NOTCH-DELTA pairs formed on the boundaries with its neighbors, which is proportional to the length of the boundaries. Right – Simulations of the model over disordered cell lattices showed that smaller cells are more likely to become high DELTA cells (red). (C) Contact area can influence differentiation of cell pairs in the fly intestine. In the fly intestine, intestinal stem cells (ISC) divide and differentiate into either self-renewing ISC (red, high DELTA) or to enteroblasts (EB, green, low DELTA). The fates of the two daughter cells is determined by the lateral inhibition process and depends of the contact area between the two cells. The three possible final states are: ISC-ISC, in case of small contact area; EB-EB, in the case of large contact area; and ISC-EB, in the case of intermediate contact area. (D) Cell shape biases differentiation of daughter cells after mitosis in zebrafish neurogenesis. A schematic of a model for a lateral inhibition process which is biased by cell shape. Before mitosis, the concentration of DELTA is higher on the elongated side of the cell and lower on the round side of the cell. The asymmetry in DELTA concentration is maintained during mitosis and biases the lateral inhibition process so that the progenitor from the elongated side adopts the V2a fate (red) and the progenitor from the round side adopts the V2b fate (green).