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

Abstract

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

Role of the boundary in feather bud formation on one-dimensional bioengineered skin

“…These results also indicated the fragility of the third bud between a pair of primary buds under the influence of mechanical stress such as the change in the skin curvature. 31 In addition, we confirmed that morphogens inducing directionality of the feather bud tilting, reflecting AP asymmetry, exist inside a native epithelium because the bud tilt disappeared in our bioengineered skin samples after reassembling single epithelial cells.…”

“…67 Similar to the mechanical effects, in the recent report by Shyer et al, it was found that the cellular self-organization and mechanosensation initiated the follicle and pattern formation. 31 This observation indicates that the mechanical instability is accompanied by reaction-diffusion instability, where the activator and the inhibitor are mechanical cellular contractility and substrate stiffness, respectively. On the developed bioengineered skin, the contractility and stiffness likely differ near the edge as compared to the center because of the 1-D mesenchyme geometry attached to the oval shape epithelium.…”

“…If mechanical stimuli can modify the bud pattern, these models will be the first-choice for reflecting a modified pattern, where cellular contractility is considered as an activator and substrate stiffness as an inhibitor in the Turing model. 31 There were some discrepancies between the experimental observations and numerical simulations. As described in the Results section, the bud number overlapped with the skin length as shown in Fig.…”

“…It is noteworthy that the reconstruction assay showed that bud formation is initiated by cell aggregation under the influence of mechanical tractability. 31 However, this reconstruction assay leaves anterior-posterior (AP) asymmetry on the engineered skins as the buds are tilted in the same direction, presumably because the native epithelium contains positional information for AP asymmetry. 29,30,[32][33][34][35] To prepare completely homogeneous bioengineered skins, we attempted to dissociate both the epithelium and the mesenchyme into single cells before reconstructing them.…”

Coordinated morphogenesis through tension-induced planar polarity

“…Tissue mechanics and force transmission have previously been involved in drosophila wing morphogenesis where the wing hinge retraction enables PCP rearrangement from a radial to a proximal-distal-oriented polarity in the wing blade (Aigouy et al, 2010); similarly a mechanical input has been implicated in setting up planar polarity during drosophila germ-band extension (Butler et al, 2009;Collinet et al, 2015;Simoes Sde et al, 2010). In a different context a recent study demonstrated that a physical pressure exerted by proliferating dermal cells controls the patterning of the avian skin (Shyer et al, 2017). However in all these examples the tissuewide tension is generated in parallel with the target tissue, while during C. elegans morphogenesis the tension generated by muscles is perpendicular to the local tension exerted by actin.…”