The Scf/Kit pathway implements self-organized epithelial patterning
Abstract
How individual cell behaviours lead to the emergence of global patterns 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 both experiments and mathematical modelling, we show that this transition from random to ordered distribution relies on mutual repulsion among motile immature MCCs, and affinity towards outer-layer intercellular junctions. Consistently, Arp2/3-mediated actin remodelling is required for MCC pattern emergence. Using multiple functional approaches, 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. On the other hand, Kit expression is sufficient to confer order to a disordered heterologous cell population. Our work reveals how a single signalling system can implement self-organised large-scale patterning.
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