Skip to main content
SpringerLink
Log in

Simple Models of Lung Development

  • Chapter
  • First Online:
Engineering Translational Models of Lung Homeostasis and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1413))

  • 600 Accesses

Abstract

Models are essential to further our understanding of lung development and regeneration and to facilitate identification and testing of potential treatments for lung diseases. A wide variety of rodent and human models are available that recapitulate one or more stages of lung development. This chapter describes the existing ‘simple’ in vitro, in silico and ex vivo models of lung development. We define which stage(s) of development each model recapitulates and highlight their pros and cons.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ahmadvand, N., Lingampally, A., Khosravi, F., Vazquez-Armendariz, A. I., Rivetti, S., Jones, M. R., Wilhelm, J., Herold, S., Barreto, G., Koepke, J., Samakovlis, C., Carraro, G., Zhang, J. S., Al Alam, D. & Bellusci, S. 2022. Fgfr2b signaling is essential for the maintenance of the alveolar epithelial type 2 lineage during lung homeostasis in mice. Cell Mol Life Sci, 79, 302.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Akram, K. M., Yates, L.L., Rothery, S., Gaboriou, D., Sanderson, J., Hind, M., Gfiffiths, M., Dean C.H. 2018. Live imaging of alveologenesis reveals dynamic epithelial cell behaviour. Nature Communications, In revision.

    Google Scholar 

  3. Alysandratos, K. D., Herriges, M. J. & Kotton, D. N. 2021. Epithelial Stem and Progenitor Cells in Lung Repair and Regeneration. Annu Rev Physiol, 83, 529–550.

    CAS  PubMed  Google Scholar 

  4. Archer, F., Bobet-Erny, A. & Gomes, M. 2021. State of the art on lung organoids in mammals. Vet Res, 52, 77.

    PubMed  PubMed Central  Google Scholar 

  5. Barkauskas, C. E., Chung, M. I., Fioret, B., Gao, X., Katsura, H. & Hogan, B. L. 2017. Lung organoids: current uses and future promise. Development, 144, 986–997.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Basil, M. C. & Morrisey, E. E. 2020. Lung regeneration: a tale of mice and men. Semin Cell Dev Biol, 100, 88–100.

    CAS  PubMed  Google Scholar 

  7. Branchfield, K., Li, R., Lungova, V., Verheyden, J. M., Mcculley, D. & Sun, X. 2016. A three-dimensional study of alveologenesis in mouse lung. Dev Biol, 409, 429–41.

    CAS  PubMed  Google Scholar 

  8. Brzoska, H. L., d’Esposito, A. M., Kolatsi-Joannou, M., Patel, V., Igarashi, P., Lei, Y., Finnell, R. H., Lythgoe, M. F., Woolf, A. S., Papakrivopoulou, E. & Long, D. A. 2016. Planar cell polarity genes Celsr1 and Vangl2 are necessary for kidney growth, differentiation, and rostrocaudal patterning. Kidney Int, 90, 1274–1284.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Butler, C. R., Hynds, R. E., Gowers, K. H., Lee Ddo, H., Brown, J. M., Crowley, C., Teixeira, V. H., Smith, C. M., Urbani, L., Hamilton, N. J., Thakrar, R. M., Booth, H. L., Birchall, M. A., De Coppi, P., Giangreco, A., O’Callaghan, C. & Janes, S. M. 2016. Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering. Am J Respir Crit Care Med, 194, 156–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Butler, J. P., Loring, S. H., Patz, S., Tsuda, A., Yablonskiy, D. A. & Mentzer, S. J. 2012. Evidence for adult lung growth in humans. The New England journal of medicine, 367, 244–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Celliere, G., Menshykau, D. & Iber, D. 2012. Simulations demonstrate a simple network to be sufficient to control branch point selection, smooth muscle and vasculature formation during lung branching morphogenesis. Biol Open, 1, 775–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Del Moral, P. M. & Warburton, D. 2010. Explant culture of mouse embryonic whole lung, isolated epithelium, or mesenchyme under chemically defined conditions as a system to evaluate the molecular mechanism of branching morphogenesis and cellular differentiation. Methods Mol Biol, 633, 71–9.

    PubMed  PubMed Central  Google Scholar 

  13. Ebisudani, T., Sugimoto, S., Haga, K., Mitsuishi, A., Takai-Todaka, R., Fujii, M., Toshimitsu, K., Hamamoto, J., Sugihara, K., Hishida, T., Asamura, H., Fukunaga, K., Yasuda, H., Katayama, K. & Sato, T. 2021. Direct derivation of human alveolospheres for SARS-CoV-2 infection modeling and drug screening. Cell Rep, 35, 109218.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Franzdottir, S. R., Axelsson, I. T., Arason, A. J., Baldursson, O., Gudjonsson, T. & Magnusson, M. K. 2010. Airway branching morphogenesis in three dimensional culture. Respir Res, 11, 162.

    PubMed  PubMed Central  Google Scholar 

  15. Gebb, S. A. & Jones, P. L. 2003. Hypoxia and lung branching morphogenesis. Adv Exp Med Biol, 543, 117–25.

    CAS  PubMed  Google Scholar 

  16. Goodwin, K. & Nelson, C. M. 2020. Branching morphogenesis. Development, 147.

    Google Scholar 

  17. Herriges, M. & Morrisey, E. E. 2014. Lung development: orchestrating the generation and regeneration of a complex organ. Development, 141, 502–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Hines, E. A. & Sun, X. 2014. Tissue crosstalk in lung development. J Cell Biochem, 115, 1469–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Hynds, R. E., Butler, C. R., Janes, S. M. & Giangreco, A. 2019. Expansion of Human Airway Basal Stem Cells and Their Differentiation as 3D Tracheospheres. Methods Mol Biol, 1576, 43–53.

    CAS  PubMed  Google Scholar 

  20. Iber, D. & Menshykau, D. 2013. The control of branching morphogenesis. Open Biol, 3, 130088.

    PubMed  PubMed Central  Google Scholar 

  21. Kina, Y. P., Khadim, A., Seeger, W. & El Agha, E. 2020. The Lung Vasculature: A Driver or Passenger in Lung Branching Morphogenesis? Front Cell Dev Biol, 8, 623868.

    PubMed  Google Scholar 

  22. Li, J., Wang, Z., Chu, Q., Jiang, K., Li, J. & Tang, N. 2018. The Strength of Mechanical Forces Determines the Differentiation of Alveolar Epithelial Cells. Dev Cell, 44, 297–312 e5.

    Google Scholar 

  23. Looney, M. R., Thornton, E. E., Sen, D., Lamm, W. J., Glenny, R. W. & Krummel, M. F. 2011. Stabilized imaging of immune surveillance in the mouse lung. Nat Methods, 8, 91–6.

    CAS  PubMed  Google Scholar 

  24. Menshykau, D., Blanc, P., Unal, E., Sapin, V. & Iber, D. 2014. An interplay of geometry and signaling enables robust lung branching morphogenesis. Development, 141, 4526–36.

    CAS  PubMed  Google Scholar 

  25. Metzger, R. J., Klein, O. D., Martin, G. R. & Krasnow, M. A. 2008. The branching programme of mouse lung development. Nature, 453, 745–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Miller, A. J. & Spence, J. R. 2017. In Vitro Models to Study Human Lung Development, Disease and Homeostasis. Physiology (Bethesda), 32, 246–260.

    CAS  PubMed  Google Scholar 

  27. Miura, T. & Shiota, K. 2000. Time-lapse observation of branching morphogenesis of the lung bud epithelium in mesenchyme-free culture and its relationship with the localization of actin filaments. Int J Dev Biol, 44, 899–902.

    CAS  PubMed  Google Scholar 

  28. Mullassery, D. & Smith, N. P. 2015. Lung development. Semin Pediatr Surg, 24, 152–5.

    PubMed  Google Scholar 

  29. Nikolic, M. Z., Caritg, O., Jeng, Q., Johnson, J. A., Sun, D., Howell, K. J., Brady, J. L., Laresgoiti, U., Allen, G., Butler, R., Zilbauer, M., Giangreco, A. & Rawlins, E. L. 2017. Human embryonic lung epithelial tips are multipotent progenitors that can be expanded in vitro as long-term self-renewing organoids. Elife, 6.

    Google Scholar 

  30. Nikolic, M. Z. & Rawlins, E. L. 2017. Lung Organoids and Their Use To Study Cell-Cell Interaction. Curr Pathobiol Rep, 5, 223–231.

    PubMed  PubMed Central  Google Scholar 

  31. Nikolic, M. Z., Sun, D. & Rawlins, E. L. 2018. Human lung development: recent progress and new challenges. Development, 145.

    Google Scholar 

  32. Nogawa, H. & Ito, T. 1995. Branching morphogenesis of embryonic mouse lung epithelium in mesenchyme-free culture. Development, 121, 1015–22.

    CAS  PubMed  Google Scholar 

  33. Parekh, K. R., Nawroth, J., Pai, A., Busch, S. M., Senger, C. N. & Ryan, A. L. 2020. Stem cells and lung regeneration. Am J Physiol Cell Physiol, 319, C675-C693.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Rock, J. & Konigshoff, M. 2012. Endogenous lung regeneration: potential and limitations. American journal of respiratory and critical care medicine, 186, 1213–9.

    CAS  PubMed  Google Scholar 

  35. Rock, J. R., Onaitis, M. W., Rawlins, E. L., Lu, Y., Clark, C. P., Xue, Y., Randell, S. H. & Hogan, B. L. 2009. Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci U S A, 106, 12771–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Schnatwinkel, C. & Niswander, L. 2013. Multiparametric image analysis of lung-branching morphogenesis. Dev Dyn, 242, 622–37.

    CAS  PubMed  Google Scholar 

  37. Short, K., Hodson, M. & Smyth, I. 2013. Spatial mapping and quantification of developmental branching morphogenesis. Development, 140, 471–8.

    CAS  PubMed  Google Scholar 

  38. Tadokoro, T., Gao, X., Hong, C. C., Hotten, D. & Hogan, B. L. 2016. Bmp signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors. Development, 143, 764–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Tadokoro, T., Wang, Y., Barak, L. S., Bai, Y., Randell, S. H. & Hogan, B. L. 2014. IL-6/STAT3 promotes regeneration of airway ciliated cells from basal stem cells. Proc Natl Acad Sci U S A, 111, E3641–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Wansleeben, C., Bowie, E., Hotten, D. F., Yu, Y. R. & Hogan, B. L. 2014. Age-related changes in the cellular composition and epithelial organization of the mouse trachea. PLoS One, 9, e93496.

    PubMed  PubMed Central  Google Scholar 

  41. Warburton, D. 2021. Conserved Mechanisms in the Formation of the Airways and Alveoli of the Lung. Front Cell Dev Biol, 9, 662059.

    PubMed  PubMed Central  Google Scholar 

  42. Warburton, D., Bellusci, S., De Langhe, S., Del Moral, P. M., Fleury, V., Mailleux, A., Tefft, D., Unbekandt, M., Wang, K. & Shi, W. 2005. Molecular mechanisms of early lung specification and branching morphogenesis. Pediatric research, 57, 26R-37R.

    PubMed  Google Scholar 

  43. Warburton, D., El-Hashash, A., Carraro, G., Tiozzo, C., Sala, F., Rogers, O., De Langhe, S., Kemp, P. J., Riccardi, D., Torday, J., Bellusci, S., Shi, W., Lubkin, S. R. & Jesudason, E. 2010a. Lung organogenesis. Current topics in developmental biology, 90, 73–158.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Warburton, D., El-Hashash, A., Carraro, G., Tiozzo, C., Sala, F., Rogers, O., De Langhe, S., Kemp, P. J., Riccardi, D., Torday, J., Bellusci, S., Shi, W., Lubkin, S. R. & Jesudason, E. 2010b. Lung organogenesis. Curr Top Dev Biol, 90, 73–158.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Yates, L. L., Schnatwinkel, C., Hazelwood, L., Chessum, L., Paudyal, A., Hilton, H., Romero, M. R., Wilde, J., Bogani, D., Sanderson, J., Formstone, C., Murdoch, J. N., Niswander, L. A., Greenfield, A. & Dean, C. H. 2013. Scribble is required for normal epithelial cell-cell contacts and lumen morphogenesis in the mammalian lung. Dev Biol, 373, 267–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Yeganeh, B., Bilodeau, C. & Post, M. 2018. Explant Culture for Studying Lung Development. Methods Mol Biol, 1752, 81–90.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Figures were created using Biorender.com.

Author information

Authors and Affiliations

  1. National Heart and Lung Institute, Imperial College London, London, UK

    Charlotte H. Dean & Sek-Shir Cheong

Authors
  1. Charlotte H. Dean
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sek-Shir Cheong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charlotte H. Dean .

Editor information

Editors and Affiliations

  1. University of Colorado, Denver | Anschutz Medical Campus, Aurora, CO, USA

    Chelsea M. Magin

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dean, C.H., Cheong, SS. (2023). Simple Models of Lung Development. In: Magin, C.M. (eds) Engineering Translational Models of Lung Homeostasis and Disease. Advances in Experimental Medicine and Biology, vol 1413. Springer, Cham. https://doi.org/10.1007/978-3-031-26625-6_2

Download citation

Publish with us

Policies and ethics

Search

Navigation