Belmonte, J. | Search bioRxiv

bioRxiv2017

Fibroblast state switching orchestrates dermal maturation and wound healing

Murine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here we propose a model in which a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determines dermal architecture. Virtual-tissue simulations of our model faithfully recapitulate dermal maturation, predicting a loss of spatial segregation of fibroblast lineages and dictating that fibroblast migration is only required for wound healing. To test this, we performed in vivo live imaging of dermal fibroblasts, which revealed that homeostatic tissue architecture is achieved without active cell migration. In contrast, both fibroblast proliferation and migration are key determinants of tissue repair following wounding. The results show that tissue-scale coordination is driven by the interdependence of cell proliferation and ECM deposition, paving the way for identifying new therapeutic strategies to enhance skin regeneration.\n\nStandfirst textWe show that fibroblast behaviour switching between two distinct states - proliferating and depositing ECM - is necessary and sufficient to define dermal architecture. Understanding this interdependence is critical for identifying new therapeutic strategies to enhance skin regeneration.\n\nHighlightsO_LITissue-scale coordination in murine dermis is driven by the interdependence of cell proliferation and ECM deposition\nC_LIO_LIThe tissue architecture is set by a negative feedback loop between ECM deposition/remodelling and proliferation\nC_LIO_LIFibroblast lineages lose segregation with age\nC_LIO_LIFibroblast migration is the critical discriminator between dermal development and wound healing\nC_LI

systems biology↗

bioRxiv2017

A Theory That Predicts Behaviors Of Disordered Cytoskeletal Networks

Morphogenesis in animal tissues is largely driven by tensions of actomyosin networks, generated by an active contractile process that can be reconstituted in vitro. Although the network components and their properties are known, the requirements for contractility are still poorly understood. Here, we describe a theory that predicts whether an isotropic network will contract, expand, or conserve its dimensions. This analytical theory correctly predicts the behavior of simulated networks consisting of filaments with varying combinations of connectors, and reveals conditions under which networks of rigid filaments are either contractile or expansile. Our results suggest that pulsatility is an intrinsic behavior of contractile networks if the filaments are not stable but turn over. The theory offers a unifying framework to think about mechanisms of contractions or expansion. It provides a foundation for the study of a broad range of processes involving cytoskeletal networks, and a basis for designing synthetic networks.

cell biology↗