Mammalian lung development: Interactions in formation and morphogenesis of tracheal buds

Wessells, Norman K.

doi:10.1002/jez.1401750405

Cited by 268 publications

(108 citation statements)

References 11 publications

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“…However, it is becoming clear that different fibroblast can have distinct functions. For example, during lung development, epithelial induction capacities are known to differ based on whether the mesenchyme is derived from the trachea or the tips of the growing lungs 69 . The origin of the mesenchymal fibroblasts apparently determines their sensitivity to sonic hedgehog (Shh) derived from the developing lung epithelia.…”

Section: Not All Fibroblasts Are Created Equalmentioning

confidence: 99%

Stromal fibroblasts in cancer initiation and progression

Bhowmick

Neilson

Moses

2004

Nature

2,045

1,700

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PrefaceIt is widely accepted that the development of carcinomas, the most common type of human cancer, is due to accumulation of somatic mutations in epithelial cells. The behavior of carcinomas is also influenced by the tumour microenvironment that includes extracellular matrix, blood vasculature, inflammatory cells and fibroblasts. Recent studies reveal that fibroblasts have a more profound influence on the development and progression of carcinomas than previously appreciated. These new findings also have therapeutic implications.Work over the past two decades have delineated the genetic lesions that occur in epithelial cells leading to the initiation and progression of carcinomas, the most common form of human cancer 1 . The discoveries of genetic changes in somatic cancer cells have not only advanced our basic understanding of tumour formation but also significantly influenced the treatment of cancer with the use of new therapies targeted to specific pathways affected by genetic lesions (see Overview).Carcinoma cells, like normal epithelial cells, live in a complex microenvironment that includes the extracellular matrix (ECM), diffusible growth factors and cytokines, and a variety of non-epithelial cell types, including those comprising the vasculature (endothelial cells, pericytes, smooth muscle cells), those that can respond to infection and injury (lymphocytes, macrophages, mast cells), and fibroblasts. It has long been recognized that carcinomas induce a modified stroma through expression of growth factors that promotes angiogenesis, altered ECM expression, accelerated fibroblast proliferation, and increased inflammatory cell recruitment 2, 3 (Figure 1).Blood vessels are a critical component of the tumour microenvironment. Without formation of new blood vessels, carcinomas cannot grow beyond a very small size or metastasize and reform in distant organs 4 . Tumour angiogenesis is due in part to secretion of endothelial growth factors by tumours, and indeed, a targeted therapy (Avastin) that blocks the action of one of these factors (VEGF) has recently been approved (see also Overview) 5 .There is also a functional relationship between inflammation and cancer9. Cancers frequently arise in areas of chronic inflammation [see also review article by Beachy]. Examples include colon carcinoma associated with inflammatory bowel disease, stomach cancer in H. pylori infection, and hepatocellular carcinomas in hepatitis C infection. Inflammatory cells are also a key component of the microenvironment of carcinomas arising * To whom Correspondence should be addressed. 649 Preston Research Building, Nashville, TN 37232, hal.moses@vanderbilt.edu. NIH Public Access Author ManuscriptNature. Author manuscript; available in PMC 2011 March 8. The three-dimensional structure supporting epithelia through the ECM is critically important, and impaired interactions of epithelial cells with ECM can result in transformation of the epithelia 6,7 . The specialized ECM that separates the epithelial and endothelial cells from the strom...

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Section: Not All Fibroblasts Are Created Equalmentioning

confidence: 99%

Stromal fibroblasts in cancer initiation and progression

Bhowmick

Neilson

Moses

2004

Nature

2,045

1,700

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“…The embryonic airway epithelium is highly proliferative in vivo (21), and it is often assumed that new branches result from localized growth (22). We therefore quantified 3D patterns of proliferation within mesenchyme-free explants ( Fig.…”

Section: Spatial Patterns Of Proliferation Do Not Appear Until Branchmentioning

confidence: 99%

Mechanically patterning the embryonic airway epithelium

Varner

Gleghorn

Miller

et al. 2015

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

106

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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...

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“…Then epithelia alone or in combination with homologous or heterologous mesenchyme were cultured in vitro or grafted into the anterior eye chamber or under the kidney capsule. It was concluded that the mesenchyme plays critical roles in organogenesis in kidney (5), pancreas (6,7), tooth (8,9), mammary gland (10), lung (11), gastrointestine (12), male urogenital tract (13,14), and female reproductive tract (15,16) tissues. In the 1970s, a search for epithelial cell-fate-determining factors of mesenchymal origin was begun, but has been without success (17)(18)(19).…”

mentioning

confidence: 99%

Follistatin-like-1, a diffusible mesenchymal factor determines the fate of epithelium

Umezu

Yamanouchi

Iida

et al. 2010

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

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Mesenchyme is generally believed to play critical roles in "secondary induction" during organogenesis. Because of the complexity of tissue interactions in secondary inductions, however, little is known about the precise mechanisms at the cellular and molecular levels. We have demonstrated that, in mouse oviductal development, the mesenchyme determines the fate of undetermined epithelial cells to become secretory or cilial cells. We have established a model for studying secondary induction by establishing clonal epithelial and mesenchymal cell lines from perinatal p53 −/− mouse oviducts. The signal sequence trap method collected candidate molecules secreted from mesenchymal cell lines. Naive epithelial cells exposed to Follistatin-like-1 (Fstl1), one of the candidates, became irreversibly committed to expressing a cilial epithelial marker and differentiated into ciliated cells. We concluded that Fstl1 is one of the mesenchymal factors determining oviductal epithelial cell fate. This is a unique demonstration that the determination of epithelial cell fate is induced by a single diffusible factor.cell fate determination | epithelial-mesenchymal interaction | Follistatinlike-1 | oviduct

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Mammalian lung development: Interactions in formation and morphogenesis of tracheal buds

Cited by 268 publications

References 11 publications

Stromal fibroblasts in cancer initiation and progression

Stromal fibroblasts in cancer initiation and progression

Mechanically patterning the embryonic airway epithelium

Follistatin-like-1, a diffusible mesenchymal factor determines the fate of epithelium

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