Complex migration rules upon contact can lead to directed mesenchymal self-patterning. (A) Different interaction modes—some speculative—by which two mesenchymal cells may respond to cell–cell contact through localized modulation of protrusion and retraction dynamics. These responses can be broadly categorized into short-range modes, such as CIL, collision guidance, and contact following, and long-range modes involving cytonemes or cytoneme-like structures such as airinemes, which also allow contact-based attraction. Each mode can operate symmetrically or asymmetrically, or even as hybrid combinations. The examples presented here illustrate the basic principles, but many additional interaction rules are conceivable. Further, regulation of mesenchymal and epithelial local properties can, instead of driving migration, also affect cell shape. (B) Conceptual model of how defined homo- and heterotypic interaction rules can give rise to complex patterns in the absence of external cues—a process we term directed mesenchymal self-patterning. (B1) In heterotypic cell populations, (B2) different cell pairings may engage in specific combinations of the contact responses summarized in (A). These interaction “rules” may vary depending on position, microenvironment, or developmental time. (B3) Such rules can generate complex, directed swarm-like behaviors, (B4) which in turn can drive stereotyped rearrangements and the emergence of specific spatial patterns. Spatial variation in these rules could also account for regional pattern differences.