Desmosomes polarize and integrate chemical and mechanical signaling to govern epidermal tissue form and function

2021 ◽  
Author(s):  
Joshua A. Broussard ◽  
Jennifer L. Koetsier ◽  
Marihan Hegazy ◽  
Kathleen J. Green
2020 ◽  
Author(s):  
Joshua Allen Broussard ◽  
Jennifer L. Koetsier ◽  
Kathleen J. Green

Open Biology ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 200360
Author(s):  
Nargess Khalilgharibi ◽  
Yanlan Mao

The basement membrane (BM) is a special type of extracellular matrix that lines the basal side of epithelial and endothelial tissues. Functionally, the BM is important for providing physical and biochemical cues to the overlying cells, sculpting the tissue into its correct size and shape. In this review, we focus on recent studies that have unveiled the complex mechanical properties of the BM. We discuss how these properties can change during development, homeostasis and disease via different molecular mechanisms, and the subsequent impact on tissue form and function in a variety of organisms. We also explore how better characterization of BM mechanics can contribute to disease diagnosis and treatment, as well as development of better in silico and in vitro models that not only impact the fields of tissue engineering and regenerative medicine, but can also reduce the use of animals in research.


2018 ◽  
Vol 106 ◽  
pp. 37-45 ◽  
Author(s):  
Carolina Baraldi A. Restini ◽  
Alex Ismail ◽  
Ramya K. Kumar ◽  
Robert Burnett ◽  
Hannah Garver ◽  
...  

Science ◽  
2021 ◽  
Vol 372 (6540) ◽  
pp. eaba2374 ◽  
Author(s):  
Shamik Mascharak ◽  
Heather E. desJardins-Park ◽  
Michael F. Davitt ◽  
Michelle Griffin ◽  
Mimi R. Borrelli ◽  
...  

Skin scarring, the end result of adult wound healing, is detrimental to tissue form and function. Engrailed-1 lineage–positive fibroblasts (EPFs) are known to function in scarring, but Engrailed-1 lineage–negative fibroblasts (ENFs) remain poorly characterized. Using cell transplantation and transgenic mouse models, we identified a dermal ENF subpopulation that gives rise to postnatally derived EPFs by activating Engrailed-1 expression during adult wound healing. By studying ENF responses to substrate mechanics, we found that mechanical tension drives Engrailed-1 activation via canonical mechanotransduction signaling. Finally, we showed that blocking mechanotransduction signaling with either verteporfin, an inhibitor of Yes-associated protein (YAP), or fibroblast-specific transgenic YAP knockout prevents Engrailed-1 activation and promotes wound regeneration by ENFs, with recovery of skin appendages, ultrastructure, and mechanical strength. This finding suggests that there are two possible outcomes to postnatal wound healing: a fibrotic response (EPF-mediated) and a regenerative response (ENF-mediated).


Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 939
Author(s):  
Kelvin W. Pond ◽  
Konstantin Doubrovinski ◽  
Curtis A. Thorne

Across metazoans, animal body structures and tissues exist in robust patterns that arise seemingly out of stochasticity of a few early cells in the embryo. These patterns ensure proper tissue form and function during early embryogenesis, development, homeostasis, and regeneration. Fundamental questions are how these patterns are generated and maintained during tissue homeostasis and regeneration. Though fascinating scientists for generations, these ideas remain poorly understood. Today, it is apparent that the Wnt/β-catenin pathway plays a central role in tissue patterning. Wnt proteins are small diffusible morphogens which are essential for cell type specification and patterning of tissues. In this review, we highlight several mechanisms described where the spatial properties of Wnt/β-catenin signaling are controlled, allowing them to work in combination with other diffusible molecules to control tissue patterning. We discuss examples of this self-patterning behavior during development and adult tissues’ maintenance. The combination of new physiological culture systems, mathematical approaches, and synthetic biology will continue to fuel discoveries about how tissues are patterned. These insights are critical for understanding the intricate interplay of core patterning signals and how they become disrupted in disease.


Author(s):  
Patricia G. Arscott ◽  
Gil Lee ◽  
Victor A. Bloomfield ◽  
D. Fennell Evans

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).


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