The Scf/Kit pathway implements self-organized epithelial patterning

Abstract

How global patterns emerge from individual cell behaviors is poorly understood. In the Xenopus embryonic epidermis, multiciliated cells (MCCs) are born in a random pattern within an inner mesenchymal layer and subsequently intercalate at regular intervals into an outer epithelial layer. Using video microscopy and mathematical modeling, we found that regular pattern emergence involves mutual repulsion among motile immature MCCs and affinity toward outer-layer intercellular junctions. Consistently, Arp2/3-mediated actin remodeling is required for MCC patterning. Mechanistically, we show that the Kit tyrosine kinase receptor, expressed in MCCs, and its ligand Scf, expressed in outer-layer cells, are both required for regular MCC distribution. Membrane-associated Scf behaves as a potent adhesive cue for MCCs, while its soluble form promotes their mutual repulsion. Finally, Kit expression is sufficient to confer order to a disordered heterologous cell population. This work reveals how a single signaling system can implement self-organized large-scale patterning.

Keywords: Scf/Kit; Xenopus; actin cytoskeleton; adhesion; cell motility; cell-cell repulsion; ciliated epithelium; contact inhibition of locomotion; pattern formation; self-organization.