Symmetry breaking of tissue mechanics in wound induced hair follicle regeneration of laboratory and spiny mice

Abstract

Tissue regeneration is a process that recapitulates and restores organ structure and function. Although previous studies have demonstrated wound-induced hair neogenesis (WIHN) in laboratory mice (Mus), the regeneration is limited to the center of the wound unlike those observed in African spiny (Acomys) mice. Tissue mechanics have been implicated as an integral part of tissue morphogenesis. Here, we use the WIHN model to investigate the mechanical and molecular responses of laboratory and African spiny mice, and report these models demonstrate opposing trends in spatiotemporal morphogenetic field formation with association to wound stiffness landscapes. Transcriptome analysis and K14-Cre-Twist1 transgenic mice show the Twist1 pathway acts as a mediator for both epidermal-dermal interactions and a competence factor for periodic patterning, differing from those used in development. We propose a Turing model based on tissue stiffness that supports a two-scale tissue mechanics process: (1) establishing a morphogenetic field within the wound bed (mm scale) and (2) symmetry breaking of the epidermis and forming periodically arranged hair primordia within the morphogenetic field (μm scale). Thus, we delineate distinct chemo-mechanical events in building a Turing morphogenesis-competent field during WIHN of laboratory and African spiny mice and identify its evo-devo advantages with perspectives for regenerative medicine.

Collective heterogeneity of mitochondrial potential in contact inhibition of proliferation

“…Hair-follicle distribution in mammalian skin is a scenario where this may be relevant. Which cells among the skin give rise to placodes and what the determining factor is still not completely understood [35, 36]. Given the density and shape changes in cells during the placode formation, it will be interesting to look at the metabolic and biophysical changes before the initiation of placode formation.…”

Furnishing Wound Repair by the Subcutaneous Fascia

“…Subcutaneous fascial tissue in the Acomys back-skin is remarkably thinner than that of the laboratory mice (Mus musculus) [74]. Acomys back-skin also exhibits lower skin biomechanics and wound tissue stiffness [76,77] as compared to the laboratory mice, which is equitable with its diminished fascial tissue. The above indicate that the abundance of the skin's subcutaneous fascia may explain the diversity seen in the skin's wound responses to injury, namely scarring or regeneration, across anatomic skin location and species.…”

Boundary Conditions Cause Different Generic Bifurcation Structures in Turing Systems

“…Critically, the changes in bifurcation structure that are produced by altering the boundary conditions from Neumann to Dirichlet are not observed in the linear analysis, which is where most application papers stop (Woolley et al 2010;Ho et al 2019;Cho et al 2011;Hans et al 2021). In this paper, we rectify this situation by demonstrating that although the Turing bifurcation is canonically a pitchfork bifurcation under Neumann boundary conditions (van Hecke et al 1994), the Turing bifurcation is canonically a transcritical bifurcation under Dirichlet boundary conditions.…”