Let's push things forward: disruptive technologies and the mechanics of tissue assembly

Varner, Victor D.; Nelson, Celeste M.

doi:10.1039/c3ib40080h

Cited by 14 publications

(15 citation statements)

References 110 publications

(223 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a sense, proliferation is "downstream" of branch initiation (22). Together, these data suggest that physical mechanisms are sufficient to pattern the morphogenesis of developing epithelia-a result that strongly asserts that material properties and mechanical cues, in addition to the well-recognized role of biochemical signals, need to be considered in studies of tissue development (38)(39)(40).…”

Section: Discussionmentioning

confidence: 94%

Mechanically patterning the embryonic airway epithelium

Varner

Gleghorn

Miller

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

106

View full text Add to dashboard Cite

Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reactiondiffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo.buckling | instability | mechanical stress | morphodynamics | morphogenesis S pace-filling, branched networks form the basic architecture of several organs, including the lung, kidney, and mammary gland. In the developing embryo, these complex structures originate as simple epithelial tubes. To form a ramified network, the initial tubular geometry is molded by a series of branching events, patterned in both space and time (1-3). In most cases, branching involves reciprocal signaling between adjacent tissues (4, 5), but it remains unclear how the locations of new branches are determined.Airway branching is highly stereotyped in the developing mouse lung (6) and regulated in part by fibroblast growth factors (FGFs) (7). New epithelial branches are thought to emerge at locations adjacent to a prepattern of focal expression of FGF10 in the neighboring mesenchyme (8, 9) (Fig. 1A), a molecular mechanism with remarkable similarity to the induction of Drosophila tracheal branching by the FGF homolog Branchless (10). Moreover, the prepattern of FGF10 is regulated by reciprocal feedback between core signaling pathways, including those downstream of sonic hedgehog, bone morphogenetic protein, Wnt, and Notch (5, 11-13). These molecular signals are thought to interact via a reaction-diffusion mechanism (14, 15) to generate the spatial template of FGF10 (16) and are typically assumed to be sufficient to pattern branch locations along the airway epithelium (5, 10). This rich molecular description, however, overlooks the role that mechanical cues might play in establishing biological patterns. The pattern of villi in the developing gut, for instance, is determined by physical buckling (17,18).When the mesenchyme is removed, thus disrupting reciprocal signaling, isolated epithelia still branch in response to FGF1 or FGF10 (19,20). In these culture models, the exogenous growth factors are present ubiquitously, with no apparent spatial pattern (Fig. 1...

show abstract

Section: Discussionmentioning

confidence: 94%

Mechanically patterning the embryonic airway epithelium

Varner

Gleghorn

Miller

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

106

View full text Add to dashboard Cite

show abstract

“…Important examples include synthetic polymer systems for 2.5D and 3D cultures 74–76 , integration of microfluidic systems in complex cultures 77–79 , cell surface-modification techniques to pattern the assembly of epithelial tissues 80 , microfabricated 3D environments to control tissue geometry and mechanics 81 and 3D pattern ing of perfused vascular networks 10,11 .…”

Section: Culture Formats For 3d Culturementioning

confidence: 99%

Three-dimensional organotypic culture: experimental models of mammalian biology and disease

Shamir

Ewald

2014

Nat Rev Mol Cell Biol

619

536

View full text Add to dashboard Cite

Mammalian organs are challenging to study as they are fairly inaccessible to experimental manipulation and optical observation. Recent advances in three-dimensional (3D) culture techniques, coupled with the ability to independently manipulate genetic and microenvironmental factors, have enabled the real-time study of mammalian tissues. These systems have been used to visualize the cellular basis of epithelial morphogenesis, to test the roles of specific genes in regulating cell behaviours within epithelial tissues and to elucidate the contribution of microenvironmental factors to normal and disease processes. Collectively, these novel models can be used to answer fundamental biological questions and generate replacement human tissues, and they enable testing of novel therapeutic approaches, often using patient-derived cells.

show abstract

“…The formation of new epithelial buds, for example, has long been thought to occur through the action of forces caused by a specific pattern of growth within the airway epithelium [37-39]. This thinking, however, relied heavily on an assumed intuitive grasp of the mechanics of branching morphogenesis, which often involves large deformations, heterogeneous tissues, and can be deceptively complex [37, 40, 41]. Recent modeling efforts have therefore worked to establish a more quantitative framework to understand the physical mechanisms of branching.…”

Section: Physical Modelsmentioning

confidence: 99%

Computational models of airway branching morphogenesis

Varner¹,

Nelson²

2017

Seminars in Cell & Developmental Biology

Self Cite

View full text Add to dashboard Cite

The bronchial network of the mammalian lung consists of millions of dichotomous branches arranged in a highly complex, space-filling tree. Recent computational models of branching morphogenesis in the lung have helped uncover the biological mechanisms that construct this ramified architecture. In this review, we focus on three different theoretical approaches – geometrical modeling, reaction-diffusion modeling, and continuum mechanical modeling – and discuss how, taken together, these models have identified the geometrical principles necessary to build an efficient bronchial network, as well as the patterning mechanisms that specify the airway geometry in the developing embryo. We emphasize models that are integrated with biological experiments and suggest how recent progress in computational modeling has advanced our understanding of airway branching morphogenesis.

show abstract

Let's push things forward: disruptive technologies and the mechanics of tissue assembly

Cited by 14 publications

References 110 publications

Mechanically patterning the embryonic airway epithelium

Mechanically patterning the embryonic airway epithelium

Three-dimensional organotypic culture: experimental models of mammalian biology and disease

Computational models of airway branching morphogenesis

Contact Info

Product

Resources

About