Epithelial-Mesenchymal Interactions in the Developing Lung
Abstract
Classical experiments in embryology have shown that normal growth, morphogenetic patterning, and cellular differentiation in the developing lung depend on interactive signaling between the endodermal epithelium and mesenchyme derived from splanchnic mesoderm. These interactions are mediated by a myriad of diffusible factors that are precisely regulated in their temporal and spatial expression. In this review we first describe factors regulating formation of the embryonic foregut. We then discuss the experiments demonstrating the importance of tissue interactions in lung patterning and differentiation. Finally, we detail the roles that a few key signaling systems-fibroblast growth factors and their receptors, sonic hedgehog and Gli genes, Wnt genes and beta-catenin, and BMP4-play as mediators of epithelial-mesenchymal interactions in the developing lung.
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Epithelial-mesenchymal interactions trigger the development of various tissues and organs through specific signaling pathways and transcription factors.
“During the early developmental stages, epithelial-mesenchymal interactions (EMIs) trigger the development of various tissues and organs through specific signaling pathways and transcription factors.”
From Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction (2022) · cites this paper as [3]
EMIs drive stomach specification, kidney duct patterning, lung development, lacrimal gland bud formation, and teeth bud formation.
“For example, EMIs drive stomach specification (1), duct patterning of the kidney (2) and lung (3), and bud formation of the lacrimal gland (4) and teeth (5).”
From Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction (2022) · cites this paper as [3]
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Torday, J. S., & Rehan, V. K. (2007) · Pediatric Research · doi:10.1203/pdr.0b013e31806772a1 · Cited by 62 · see citing works
Normal and Abnormal Structural Development of the Lung
Wert, S. E. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-3479-7.10078-3 · Cited by 62 · see citing works
Identity and novelty in the avian syrinx
Kingsley, E. P., Eliason, C. M., Riede, T., Li, Z., Hiscock, T. W., Farnsworth, M. S., Thomson, S. L., Goller, F., Tabin, C. J., & Clarke, J. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804586115 · Cited by 59 · see citing works
Characterization of a mouse amelogenin [A−4]/M59 cell surface receptor
Tompkins, K. A., George, A., & Veis, A. (2005) · Bone · doi:10.1016/j.bone.2005.08.013 · Cited by 60 · see citing works
Asikainen, T. M., Ahmad, A. M., Schneider, B. K., & White, C. W. (2005) · Pediatric Pulmonology · doi:10.1002/ppul.20321 · Cited by 60 · see citing works
Anuka, E., Gal, M., Stocco, D. M., & Orly, J. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.02.003 · Cited by 60 · see citing works
Wnt signaling pathway and lung disease
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Saito, A., Nikolaidis, N. M., Amlal, H., Uehara, Y., Gardner, J. C., LaSance, K., Pitstick, L. B., Bridges, J. P., Wikenheiser‐Brokamp, K. A., McGraw, D. W., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aac8577 · Cited by 59 · see citing works
Proteoglycan and collagen expression during human air conducting system development
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Transcriptional Regulation of Perinatal Lung Maturation
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Iroquoisgenes influence proximo-distal morphogenesis during rat lung development
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Self-citationAgha, E. E., & Bellusci, S. (2014) · Scientifica · doi:10.1155/2014/538379 · Cited by 57 · see citing works
Limb Regeneration in Axolotl: Is It Superhealing?
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Parabronchial smooth muscle cells and alveolar myofibroblasts in lung development
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Self-citationMisexpression of ELF5 disrupts lung branching and inhibits epithelial differentiation
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Self-citation
- Authors
- Shannon, J. M., & Hyatt, B. A.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Venue
- Annual Review of Physiology
- Publisher
- Annual Reviews
- Published
- 2004-03-01
- Volume
- 66
- Issue
- 1
- Pages
- 625-645
- ISSN
- 0066-4278 (ISSN-L)
- 1545-1585
- OpenAlex
- W2137075665
- Cited by
- 321
- References
- 118
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 6 · 2021: 11 · 2020: 8 · 2019: 13 · 2018: 4 · 2017: 13 · 2016: 10 · 2015: 17 · 2014: 14 · 2013: 14 · 2012: 23
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL071898, P50-HL56387, P50HL056387)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Keywords
- epithelial-mesenchymal interactions, lung development, lung morphogenesis, lung differentiation, fibroblast growth factor, Sonic hedgehog, Wnt signaling, β-catenin, BMP4, splanchnic mesoderm, endodermal epithelium, signaling molecules
- MeSH terms
- Animals, Embryo, Mammalian, Endoderm, Epithelium, Embryonic and Fetal Development, Humans, Lung, Mesoderm
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