Lateral inhibition

Durant and colleagues (2016) review an older line of theory in which lateral inhibition acts over long range. Meinhardt and Gierer, inspired by Turing, proposed chemical systems with local self-activation and long-range lateral inhibition that generate patterns from near-homogeneous states². Durant et al. report that such models can explain polarity, re-patterning and scaling in planarian worms after surgery². A classic local activation and lateral inhibition model with a third diffusible molecule can match the head-tail pattern to worm length, as Werner and colleagues showed in 2015². Specific molecular components have been proposed for these mechanisms, such as cAMP and ATP, which can diffuse through gap junctions (Schiffmann 2011)².

Newman (2019) describes lateral inhibition through the Notch pathway as suited to fine-grained salt-and-pepper patterns in which adjacent cells differ⁴. Newman argues that organogenesis needs larger domains of one cell type, and that morphogen gradients can set these only if the target cells are in similar states of receptivity⁴. Newman groups morphogen induction and lateral inhibition as active, energy-consuming processes that change one kind of entity into another, and compares them to chemical transformation⁵. Davies and Cachat (2016) write that others have created synthetic Notch–Delta circuits that could be used to generate lateral-inhibition patterns in mammalian cells³. They describe their own de novo system, which uses adhesion-driven phase separation instead³.

Zakirov and colleagues (2021) used a computational model of endothelial cell selection in angiogenesis. They report that small changes in the probability of extending a filopodium delayed selection of the alternating tip and stalk pattern⁶. A reduced VEGF gradient or concentration also slowed patterning, in agreement with the precursor model⁶. Their simulations predict that increased filopodia extension can rescue patterning speed when VEGF function is reduced⁶. They note that the role of filopodia in angiogenesis has been elusive. Filopodia had earlier been described as widening the reach of cell-cell communication in Notch patterning of Drosophila bristles⁷.

Pai and colleagues (2012) cite a stochastic lateral inhibition system involving ion channels that produces lateralized neural differentiation in C. elegans¹. They call it tempting to speculate that an asymmetric bioelectric signal could trigger genetic, chemical or biophysical patterns that let the left and right sides of the visual system differ¹. Silic and Zhang (2023), reviewing chemogenetic tools, report a study in which PSAM-GlyR was expressed in zebrafish horizontal cells. Disrupting the membrane voltage of those cells altered the light response and lateral inhibition in retinal ganglion cells⁸.