Wnt/β-catenin Signaling in Tissue Self-Organization

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.

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To form and function: on the role of basement membrane mechanics in tissue development, homeostasis and disease

Open Biology ◽

10.1098/rsob.200360 ◽

2021 ◽

Vol 11 (2) ◽

pp. 200360

Author(s):

Nargess Khalilgharibi ◽

Yanlan Mao

Keyword(s):

Basement Membrane ◽

Molecular Mechanisms ◽

Disease Diagnosis ◽

Membrane Mechanics ◽

Form And Function ◽

And Function ◽

Tissue Form

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.

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239 Desmosomes pattern cell mechanics to govern epidermal tissue form and function

Journal of Investigative Dermatology ◽

10.1016/j.jid.2019.07.240 ◽

2019 ◽

Vol 139 (9) ◽

pp. S255

Author(s):

J.A. Broussard ◽

J.L. Koetsier ◽

K.J. Green

Keyword(s):

Cell Mechanics ◽

Form And Function ◽

Epidermal Tissue ◽

And Function ◽

Tissue Form

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On Growth, Form, and Function—A Fantasia on the Design of a Mammal

Journal of Dynamic Systems Measurement and Control ◽

10.1115/1.3426717 ◽

1973 ◽

Vol 95 (3) ◽

pp. 291-295 ◽

Cited By ~ 4

Author(s):

A. S. Iberall

Keyword(s):

Growth Form ◽

Large Family ◽

Living System ◽

Self Organization ◽

Entire Class ◽

Form And Function ◽

Physical Essence ◽

Design Characteristics ◽

And Function ◽

Biological Organisms

The development of a system’s biology, as a common construct for both physiologist and engineer, requires both a theory of structures (form) and a theory of dynamics (function). A dynamic organizing principle—“homeokinesis”—for the living system was proposed earlier. Based on thermodynamic reasoning, homeokinesis attempts to capture the physical essence of homeostasis. Now, a primitive foundation is proposed from which a large family of design characteristics might emerge, by self-organization, in complex biological organisms. This foundation is directed at the emergence of major form parameters of the entire class of mammalia, from 3 gm adult shrews to 100,000 kg whales.

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Form and Function of the M4 Cell, an Intrinsically Photosensitive Retinal Ganglion Cell Type Contributing to Geniculocortical Vision

Journal of Neuroscience ◽

10.1523/jneurosci.1422-12.2012 ◽

2012 ◽

Vol 32 (39) ◽

pp. 13608-13620 ◽

Cited By ~ 129

Author(s):

M. E. Estevez ◽

P. M. Fogerson ◽

M. C. Ilardi ◽

B. G. Borghuis ◽

E. Chan ◽

...

Keyword(s):

Ganglion Cell ◽

Retinal Ganglion Cell ◽

Retinal Ganglion ◽

Cell Type ◽

Form And Function ◽

And Function

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Renal perivascular adipose tissue: Form and function

Vascular Pharmacology ◽

10.1016/j.vph.2018.02.004 ◽

2018 ◽

Vol 106 ◽

pp. 37-45 ◽

Cited By ~ 10

Author(s):

Carolina Baraldi A. Restini ◽

Alex Ismail ◽

Ramya K. Kumar ◽

Robert Burnett ◽

Hannah Garver ◽

...

Keyword(s):

Adipose Tissue ◽

Perivascular Adipose Tissue ◽

Form And Function ◽

And Function ◽

Tissue Form

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Integrated and independent evolution of heteromorphic sperm types

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2013.1647 ◽

2013 ◽

Vol 280 (1769) ◽

pp. 20131647 ◽

Cited By ~ 5

Author(s):

Allen J. Moore ◽

Leonardo D. Bacigalupe ◽

Rhonda R. Snook

Keyword(s):

Reproductive Tract ◽

Developmental Process ◽

Functional Integration ◽

Genetic Correlations ◽

Female Reproductive Tract ◽

Species Variation ◽

Cell Type ◽

Form And Function ◽

And Function ◽

Sperm Traits

Sperm are a simple cell type with few components, yet they exhibit tremendous between-species morphological variation in those components thought to reflect selection in different fertilization environments. However, within a species, sperm components are expected to be selected to be functionally integrated for optimal fertilization of eggs. Here, we take advantage of within-species variation in sperm form and function to test whether sperm components are functionally and genetically integrated both within and between sperm morphologies using a quantitative genetics approach. Drosophila pseudoobscura males produce two sperm types with different functions but which positively interact together in the same fertilization environment; the long eusperm fertilizes eggs and the short parasperm appear to protect eusperm from a hostile female reproductive tract. Our analysis found that all sperm traits were heritable, but short sperm components exhibited evolvabilities 10 times that of long sperm components. Genetic correlations indicated functional integration within, but not between, sperm morphs. These results suggest that sperm, despite sharing a common developmental process, can become developmentally and functionally non-integrated, evolving into separate modules with the potential for rapid and independent responses to selection.

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Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring

Science ◽

10.1126/science.aba2374 ◽

2021 ◽

Vol 372 (6540) ◽

pp. eaba2374 ◽

Cited By ~ 1

Author(s):

Shamik Mascharak ◽

Heather E. desJardins-Park ◽

Michael F. Davitt ◽

Michelle Griffin ◽

Mimi R. Borrelli ◽

...

Keyword(s):

Wound Healing ◽

Mechanical Strength ◽

Transgenic Mouse ◽

Mouse Models ◽

Transgenic Mouse Models ◽

Fibrotic Response ◽

Mechanical Tension ◽

Form And Function ◽

And Function ◽

Tissue Form

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).

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