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Emergent cellular self-organization and mechanosensation initiate follicle pattern in the avian skin

Mechanics of follicle patterning in skin Studies of skin organogenesis have presupposed that a periodic molecular prepattern is responsible for the initiation of a periodic pattern of hair or feathers. To date, however, these initiating molecules have remained elusive. Using chicken skin as a model system, Shyer et al. found that the periodic spacing of feathers is triggered by mechanical rather than molecular events (see the Perspective by Grill). Furthermore, these mechanical events shape both the structure of prefeathers and their molecular identity. Science, this issue p. 811; see also p. 750 In developing chick skin, mechanical force establishes skin follicle patterning. The spacing of hair in mammals and feathers in birds is one of the most apparent morphological features of the skin. This pattern arises when uniform fields of progenitor cells diversify their molecular fate while adopting higher-order structure. Using the nascent skin of the developing chicken embryo as a model system, we find that morphological and molecular symmetries are simultaneously broken by an emergent process of cellular self-organization. The key initiators of heterogeneity are dermal progenitors, which spontaneously aggregate through contractility-driven cellular pulling. Concurrently, this dermal cell aggregation triggers the mechanosensitive activation of β-catenin in adjacent epidermal cells, initiating the follicle gene expression program. Taken together, this mechanism provides a means of integrating mechanical and molecular perspectives of organ formation.