Multiscale modeling of layer formation in epidermis

20Citations
Citations of this article
61Readers
Mendeley users who have this article in their library.

Abstract

The mammalian skin epidermis is a stratified epithelium composed of multiple layers of epithelial cells that exist in appropriate sizes and proportions, and with distinct boundaries separating each other. How the epidermis develops from a single layer of committed precursor cells to form a complex multilayered structure of multiple cell types remains elusive. Here, we construct stochastic, three-dimensional, and multiscale models consisting of a lineage of multiple cell types to study the control of epidermal development. Symmetric and asymmetric cell divisions, stochastic cell fate transitions within the lineage, extracellular morphogens, cell-to-cell adhesion forces, and cell signaling are included in model. A GPU algorithm was developed and implemented to accelerate the simulations. These simulations show that a balance between cell proliferation and differentiation during lineage progression is crucial for the development and maintenance of the epidermal tissue. We also find that selective intercellular adhesion is critical to sharpening the boundary between layers and to the formation of a highly ordered structure. The long-range action of a morphogen provides additional feedback regulations, enhancing the robustness of overall layer formation. Our model is built upon previous experimental findings revealing the role of Ovol transcription factors in regulating epidermal development. Direct comparisons of experimental and simulation perturbations show remarkable consistency. Taken together, our results highlight the major determinants of a well-stratified epidermis: balanced proliferation and differentiation, and a combination of both short- (symmetric/asymmetric division and selective cell adhesion) and long-range (morphogen) regulations. These underlying principles have broad implications for other developmental or regenerative processes leading to the formation of multilayered tissue structures, as well as for pathological processes such as epidermal wound healing.

Cite

CITATION STYLE

APA

Du, H., Wang, Y., Haensel, D., Lee, B., Dai, X., & Nie, Q. (2018). Multiscale modeling of layer formation in epidermis. PLoS Computational Biology, 14(2). https://doi.org/10.1371/journal.pcbi.1006006

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free