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.

In mammals, both sterile wounding and infection induce inflammation and activate the innate immune system, and the combination of both challenges may lead to severe health defects, revealing the importance of the balance between the intensity and resolution of the inflammatory response for the organism’s fitness. Underlying mechanisms remain however elusive. Using Drosophila, we show that, upon infection with the entomopathogenic bacterium Pseudomonas entomophila (Pe), a sterile wounding induces a reduced resistance and increased host mortality. To identify the molecular mechanisms underlying the susceptibility of wounded flies to bacterial infection, we analyzed the very first steps of the process by comparing the transcriptome landscape of infected (simple hit flies, SH), wounded and infected (double hit flies, DH) and wounded (control) flies. We observed that overexpressed genes in DH flies compared to SH ones are significantly enriched in genes related to stress, including members of the JNK pathway. We demonstrated that the JNK pathway plays a central role in the DH phenotype by manipulating the Jra/dJun activity. Moreover, the CrebA/Creb3-like transcription factor (TF) and its targets were up-regulated in SH flies and we show that CrebA is required for mounting an appropriate immune response. Drosophila thus appears as a relevant model to investigate interactions between trauma and infection and allows to unravel key pathways involved.

SUMMARYHow 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 chaotic 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. While Scf behaves as a potent adhesive cue for MCCs, 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.Highlights- Immature multiciliated cells transit from a disordered to an ordered pattern- The transition is a self-organising process based on repulsive and affinity movements- ARP2/3-dependent actin remodelling is required for pattern emergence- The SCF/KIT pathway promotes both repulsion and affinity movementseTOC blurbIn developing Xenopus epidermis, immature multiciliated cells (MCCs), initially chaotically distributed within an inner layer, emerge in an orderly pattern among cells of the outer layer. This process involves MCC mutual repulsion and affinity towards outer-layer intercellular junctions. The SCF/KIT signalling pathway promotes both properties to allow regular MCC distribution.

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