| Abstract: |
| Epidermal morphogenesis, which occurs during the second half of embryogenesis, is the developmental process that generates a skin permeability barrier essential for terrestrial survival. Defects with this barrier are associated with common skin disorders such as atopic dermatitis. Study of mechanisms that control epidermal development and differentiation is therefore highly relevant to human health. Motivated by recent experimental observations on the role of Ovol transcription factors in regulating epidermal development, we developed a multiscale model to investigate the underlying mechanisms responsible for epidermal layer formation and homeostasis. We report that regulation of proliferation and differentiation by Ovol plays an important role in epidermal development. In addition, our computational analysis shows that asymmetric cell division, selective cell adhesion, and morphogen regulation work in a synergetic manner to produce the well-stratified epidermal layers. Taken together, our results demonstrate that robust epidermal morphogenesis involves a balance between proliferation and differentiation, and an interplay between short- and long-range spatial control mechanisms. This principle may also be applicable to other complex systems of tissue development or regeneration. |
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