Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Eye
  • View all journals
  • Search
  • Log in
  • Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. eye
  3. articles
  4. article
Lens development
Download PDF
Download PDF
  • Article
  • Published: May 1999

Lens development

  • J W McAvoy1,
  • C G Chamberlain1,
  • R U de Longh1,
  • A M Hales1 &
  • …
  • F J Lovicu1 

Eye volume 13, pages 425–437 (1999)Cite this article

  • 10k Accesses

  • 220 Citations

  • Metrics details

Abstract

This review gives a brief account of the main processes of lens development, including induction, morphogenesis, differentiation and growth. It describes what is known about the molecules and mechanisms that control and regulate these processes. Some of the recent progress made in understanding the molecular basis of lens development is highlighted along with some of the challenging areas for future research.

Similar content being viewed by others

Three-dimensional data capture and analysis of intact eye lenses evidences emmetropia-associated changes in epithelial cell organization

Article Open access 09 October 2020

Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract

Article Open access 26 January 2021

Multimodal spatiotemporal phenotyping of human retinal organoid development

Article Open access 08 May 2023

Article PDF

References

  1. Spemann H . Über correlation in der Enwickelung des Auges. Verh Anat Ges 1901;15:61–79.

    Google Scholar 

  2. McAvoy JW . Developmental biology of the lens. In: Duncan G, editor. Mechanisms of cataract formation in the human lens. London: Academic Press, 1981:7–46.

  3. Jacobson AG . Inductive processes in embryonic development. Science 1966;152:25–34.

    Article  CAS  Google Scholar 

  4. Grainger RM, Mannion JE, Cook TL Jr, Zygar CA . Defining intermediate stages in cell determination: acquisition of a lens-forming bias in head ectoderm during lens determination. Dev Genet 1997;20:246–57.

    Article  CAS  Google Scholar 

  5. Saha MS, Servetnick M, Grainger RM . Vertebrate eye development. Curr Biol 1992;2:582–8.

    Article  CAS  Google Scholar 

  6. Haider G, Callaerts P, Gehring WJ . Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 1995;267:1788–92.

    Article  Google Scholar 

  7. Altmann CR, Chow RL, Lang RA, Hemmati-Brivanlou A . Lens induction by Pax-6 in Xenopus laevis. Dev Biol 1997;185:119–23.

    Article  CAS  Google Scholar 

  8. Grindley IG, Davidson DR, Hill RE . The role of Pax-6 in eye and nasal development. Development 1995;121:1433–42.

    CAS  PubMed  Google Scholar 

  9. Stadler HS, Solursh M . Characterisation of the homeobox-containing gene GH6 identifies novel regions of homeobox gene expression in the developing chick embryo. Dev Biol 1994;161:251–62.

    Article  Google Scholar 

  10. Bonini NM, Bui QT, Gray-Board GL, Warrick JM . The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates. Development 1997;124:4819–26.

    CAS  PubMed  Google Scholar 

  11. Yoshida K, Imaki J, Koyama Y, Harada T, Shinmei Y, Oishi C, et al. Differential expression of maf-1 and maf-2 genes in the developing rat lens. Invest Ophthalmol Vis Sci 1997;38:2679–83.

    CAS  PubMed  Google Scholar 

  12. Ogino H, Yasuda K . Induction of lens differentiation by activation of a bZIP transcription factor, L-Maf. Science 1998;280:115–8.

    Article  CAS  Google Scholar 

  13. Liu Q, Ji X, Breitman ML, Hitchcock PF, Swaroop A . Expression of the bZIP transcription factor gene Nrl in the developing nervous system. Oncogene 1996;12:207–11.

    CAS  PubMed  Google Scholar 

  14. Monaghan AP, Davidson DR, Sime C, Graham E, Baldock R, Bhattacharya SS, et al. The Msh-like homeobox genes define domains in the developing vertebrae eye. Development 1991;112:1053–61.

    CAS  PubMed  Google Scholar 

  15. Foerst-Potts L, Sadler TW . Disruption of Msx-1 and Msx-2 reveals roles for these genes in craniofacial, eye, and axial development. Dev Dynam 1997;209:70–84.

    Article  CAS  Google Scholar 

  16. Oliver G, Sosa-Pineda B, Geisendorf S, Spana EP, Doe CQ, Gruss P . Prox 1, a prospero-related homeobox gene expressed during mouse development. Mech Dev 1993;44:3–16.

    Article  CAS  Google Scholar 

  17. Tomarev SI, Sundin O, Banerjee-Basu S, Duncan MK, Yang JM, Piatigorsky J . Chicken homeobox gene Prox 1 related to Drosophila prospero is expressed in the developing lens and retina. Dev Dynam 1996;206:354–67.

    Article  CAS  Google Scholar 

  18. Semina EV, Reiter RS, Murray JC . Isolation of a new homeobox gene belonging to the Pitx/Rieg family: expression during lens development and mapping to the aphakia region on mouse chromosome 19. Hum Mol Genet 1997;6:2109–16.

    Article  CAS  Google Scholar 

  19. Oliver G, Mailhos A, Wehr R, Copeland NG, Jenkins NA, Gruss P . Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 1995;121:4045–55.

    CAS  PubMed  Google Scholar 

  20. Oliver G, Loosli F, Koster R, Wittbrodt J, Gruss P . Ectopic lens induction in fish in response to the murine homeobox gene Six3. Mech Dev 1996;60:233–9.

    Article  CAS  Google Scholar 

  21. Kamachi Y, Sockanathan S, Liu Q, Breitman M, Lovell-Badge R, Kondoh H . Involvement of SOX proteins in lens-specific activation of crystallin genes. EMBO J 1995;14:3510–9.

    Article  CAS  Google Scholar 

  22. Nishiguchi S, Wood H, Kondoh H, Lovell-Badge R, Episkopou V . Soxl directly regulates the gamma-crystallin genes and is essential for lens development in mice. Genes Dev 1998;12:776–81.

    Article  CAS  Google Scholar 

  23. Pignoni F, Hu B, Zavitz KH, Xiao J, Garrity PA, Zipursky S . The eye-specification proteins So and Eya form a complex and regulate multiple steps in Drosophila eye development. Cell 1997;91:881–91.

    Article  CAS  Google Scholar 

  24. McAvoy JW . Cytoplasmic processes interconnect lens placode and optic vesicle during eye morphogenesis. Exp Eye Res 1980;31:527–34.

    Article  CAS  Google Scholar 

  25. Silver J, Hughes JFW . The role of cell death during morphogenesis of the mammalian eye. J Morphol 1973;140:159–70.

    Article  CAS  Google Scholar 

  26. Harding CV, Reddan JR, Unakar NJ, Bagchi M . The control of cell division in the ocular lens. Int Rev Cytol 1971;31:215–300.

    Article  CAS  Google Scholar 

  27. McAvoy JW . Cell division, cell elongation and distribution of α-, β- and γ-crystallins in the rat lens. J Embryol Exp Morphol 1978;44:149–65.

    CAS  PubMed  Google Scholar 

  28. McAvoy JW . Cell division, cell elongation and the coordination of crystallin gene expression during lens morphogenesis in the rat. J Embryol Exp Morphol 1978;45:271–81.

    CAS  PubMed  Google Scholar 

  29. Van Leen RW, Breuer ML, Lubsen NH, Schoenmakers JGG . Developmental expression of crystallin genes: in situ hybridisation reveals a differential localisation of specific mRNAs. Dev Biol 1987;123:338–45.

    Article  CAS  Google Scholar 

  30. Coulombre JL, Coulombre AJ . Lens development: fibre elongation and lens orientation. Science 1963;142:1489–90.

    Article  CAS  Google Scholar 

  31. Yamamoto Y . Growth of lens and ocular environment: role of neural retina in the growth of mouse lens as revealed by implantation experiment. Dev Growth Differ 1976;18:273–8.

    Article  Google Scholar 

  32. Chamberlain CG, McAvoy JW . Evidence that fibroblast growth factor promotes lens fibre differentiation. Curr Eye Res 1987;6:1165–9.

    Article  CAS  Google Scholar 

  33. Chamberlain CG, McAvoy JW . Induction of lens fibre differentiation by acidic and basic fibroblast growth factor (FGF). Growth Factors 1989;1:125–34.

    Article  CAS  Google Scholar 

  34. McAvoy JW, Chamberlain CG . Fibroblast growth factor (FGF) induces different responses in lens epithelial cells depending on its concentration. Development 1989;107:221–8.

    CAS  PubMed  Google Scholar 

  35. Lovicu FJ, McAvoy JW . Structural analysis of lens epithelial explants induced to differentiate into fibres by fibroblast growth factor (FGF). Exp Eye Res 1989;49:479–94.

    Article  CAS  Google Scholar 

  36. Lovicu FJ, McAvoy JW . The age of rats affects response of lens epithelial explants to fibroblast growth factor: an ultrastructural analysis. Invest Ophthalmol Vis Sci 1992;33:2269–78.

    CAS  PubMed  Google Scholar 

  37. Lovicu FJ, McAvoy JW . A structural analysis of fibroblast growth factor (FGF)-induced lens fibre differentiation in vitro. J Comput Assist Micros 1993;5:57–63.

    Google Scholar 

  38. Kuwabara T, Imaizumi M . Denucleation process of the lens. Invest Ophthalmol 1974;13:973–81.

    CAS  PubMed  Google Scholar 

  39. Kuwabara T . The maturation of the lens cell: a morphologic study. Exp Eye Res 1975;20:427–43.

    Article  CAS  Google Scholar 

  40. Harding CV, Susan SR, Murphy H . Scanning electron microscopy of the adult rabbit lens. Ophthalmic Res 1976;8:443–55.

    Article  Google Scholar 

  41. Richardson NA, McAvoy JW . Age-related changes in fibre differentiation of rat lens epithelial explants exposed to fibroblast growth factor. Exp Eye Res 1990;50:203–11.

    Article  CAS  Google Scholar 

  42. Richardson NA, McAvoy JW, Chamberlain CG . Age of rats affects response of lens epithelial explants to fibroblast growth factor. Exp Eye Res 1992;55:649–56.

    Article  CAS  Google Scholar 

  43. Peek R, McAvoy JW, Lubsen NH, Schoenmakers JGG . Rise and fall of crystallin gene messenger levels during fibroblast growth factor induced terminal differentiation of lens cells. Dev Biol 1992;152:152–60.

    Article  CAS  Google Scholar 

  44. Ohbayashi N, Hoshikawa M, Kimura S, Yamasaki M, Fukui S, Itoh N . Structure and expression of the mRNA encoding a novel fibroblast growth factor, FGF-18. J Biol Chem 1998;29:18161–4.

    Article  Google Scholar 

  45. Chamberlain CG, McAvoy JW . Fibre differentiation and polarity in the mammalian lens: a key role for FGF. Prog Ret Eye Res 1997;16:443–78.

    Article  CAS  Google Scholar 

  46. Lovicu FJ, de Iongh RU, McAvoy JW . Expression of FGF-1 and FGF-2 mRNA during lens morphogenesis, differentiation and growth. Curr Eye Res 1997;16:222–30.

    Article  CAS  Google Scholar 

  47. Hartung H, Feldman B, Lovec H, Coulier F, Birnbaum D, Goldfarb M . Murine FGF-12 and FGF-13: expression in embryonic nervous system, connective tissue and heart. Mech Dev 1997;64:31–9.

    Article  CAS  Google Scholar 

  48. Wilkinson DG, Bhatt S, McMahon AP . Expression patterns of the FGF-related proto-oncogene int-2 suggests multiple roles in fetal development. Development 1989;105:131–6.

    CAS  PubMed  Google Scholar 

  49. Kitaoka T, Aotaki-Keen AE, Hjelmeland LM . Distribution of FGF-5 in the rhesus macaque retina. Invest Ophthalmol Vis Sci 1994;35:3189–98.

    CAS  PubMed  Google Scholar 

  50. McAvoy JW, Chamberlain CG, de Iongh RU, Richardson NA, Lovicu FJ . The role of fibroblast growth factor in eye lens development. Ann NY Acad Sci 1991;638:256–74.

    Article  CAS  Google Scholar 

  51. Lovicu FJ, Chamberlain CG, McAvoy JW . Differential effects of aqueous and vitreous on fibre differentiation and extracellular matrix accumulation in lens epithelial explants. Invest Ophthalmol Vis Sci 1995;36:1459–69.

    CAS  PubMed  Google Scholar 

  52. Schulz MW, Chamberlain CG, de Iongh RU, McAvoy JW . Acidic and basic FGF in ocular media and lens: implications for lens polarity and growth patterns. Development 1993;118:117–26.

    CAS  PubMed  Google Scholar 

  53. Chamberlain CG, McAvoy JW, Richardson NA . The effects of insulin and basic fibroblast growth factor on fibre differentiation in rat lens epithelial explants. Growth Factors 1991;4:183–8.

    Article  CAS  Google Scholar 

  54. Richardson NA, Chamberlain CG, McAvoy JW . IGF-1 enhancement of FGF-induced lens fibre differentiation in rats of different ages. Invest Ophthalmol Vis Sci 1993;34:3303–12.

    CAS  PubMed  Google Scholar 

  55. Liu J, Chamberlain CG, McAvoy JW . IGF enhancement of FGF-induced fibre differentiation and DNA synthesis in lens explants. Exp Eye Res 1996;63:621–9.

    Article  CAS  Google Scholar 

  56. Arnold DR, Moshayedi P, Schoen TR, Jones BE, Chader GJ, Waldbillig RJ . Distribution of IGF-I and -II, IGF binding proteins (IGFBPs) and IGFBP mRNA in ocular fluids and tissues: potential sites of synthesis of IGFBPs in aqueous and vitreous. Exp Eye Res 1993;56:555–65.

    Article  CAS  Google Scholar 

  57. Johnson DE, Williams LT . Structural and functional diversity in the FGF receptor multigene family. Adv Cancer Res 1993;60:1–41.

    CAS  PubMed  Google Scholar 

  58. Orr-Urtreger A, Bedford MT, Burakova T, Arman E, Zimmer Y, Yayon A, et al. Developmental localisation of the splicing alternatives of fibroblast growth factor receptor-2 (FGFR2). Dev Biol 1993;158:475–86.

    Article  CAS  Google Scholar 

  59. Peters K, Ornitz D, Werner S, Williams L . Unique expression pattern of the FGF receptor-3 gene during mouse organogenesis. Dev Biol 1993;155:423–30.

    Article  CAS  Google Scholar 

  60. de Iongh RU, Lovicu FJ, Hanneken A, Baird A, McAvoy JW . FGF receptor-1 (fig) expression is correlated with fibre differentiation during rat lens morphogenesis. Dev Dynam 1996;206:412–26.

    Article  CAS  Google Scholar 

  61. de Iongh RU, Lovicu FJ, Chamberlain CG, McAvoy JW . Differential expression of fibroblast growth factor receptors during rat lens morphogenesis and growth. Invest Ophthalmol Vis Sci 1997;38:1688–99.

    CAS  PubMed  Google Scholar 

  62. Robinson ML, Overbeek PA, Verran DJ, Grizzle WE, Stockard CR, Friesel R, et al. Extracellular FGF-1 acts as a lens differentiation factor in transgenic mice. Development 1995;121:505–14.

    CAS  PubMed  Google Scholar 

  63. Robinson ML, Ohtaka-Maruyama C, Chan C, Jamieson S, Dickson C, Overbeek PA, et al. Disregulation of ocular morphogenesis by lens-specific expression of FGF-3/int-2 in transgenic mice. Dev Biol 1998;198:13–31.

    Article  CAS  Google Scholar 

  64. Lovicu FJ, Overbeek PA . Overlapping effects of different members of the FGF family on lens fibre differentiation in transgenic mice. Development 1998;125:3365–77.

    CAS  PubMed  Google Scholar 

  65. Srinivasan Y, Overbeek PA . Expression of lens specific fibroblast growth factor (FGF5) causes altered epithelial cell morphology and degeneration of fibre cells. Invest Ophthalmol Vis Sci (ARVO Suppl) 1996;37:S924.

    Google Scholar 

  66. Stolen CG, Jackson MK, Griep AE . Overexpression of FGF-2 modulates fibre cell differentiation and survival in the mouse lens. Development 1997;124:4009–17.

    CAS  PubMed  Google Scholar 

  67. Chow RL, Diez Roux G, Roghani M, Palmer MA, Rifkin D, Moscatelli D, et al. FGF suppresses apoptosis and induces differentiation of fibre cells in the mouse lens. Development 1995;121:4383–93.

    CAS  PubMed  Google Scholar 

  68. Robinson ML, MacMillan-Crow LA, Thompson JA, Overbeek PA . Expression of a truncated FGF receptor results in defective lens development in transgenic mice. Development 1995;121:3959–67.

    CAS  PubMed  Google Scholar 

  69. Liu J, Hales AM, Chamberlain CG, McAvoy JW . Induction of cataract-like changes in rat lens epithelial explants by transforming growth factor β. Invest Ophthalmol Vis Sci 1994;35:388–401.

    CAS  PubMed  Google Scholar 

  70. Hales AM, Chamberlain CG, McAvoy JW . Cataract induction in lenses cultured with transforming growth factor-β. Invest Ophthalmol Vis Sci 1995;36:1709–13.

    CAS  PubMed  Google Scholar 

  71. Hales AM, Chamberlain CG, Murphy CR, McAvoy JW . Estrogen protects lenses against cataract induced by transforming growth factor-β (TGFβ). J Exp Med 1997;185:273–80.

    Article  CAS  Google Scholar 

  72. McAvoy JW, Schulz MW, Maruno KA, Chamberlain CG, Lovicu FJ . TGF-β-induced cataract is characterised by epithelial-mesenchymal transition and apoptosis. Invest Ophthalmol Vis Sci (ARVO Suppl) 1998;39:S7.

    Google Scholar 

  73. de Iongh RU, Gordon-Thomson C, Chamberlain CG, McAvoy JW . Age-related competence of TGFβ response in rat lens epithelium correlates with receptor expression. Invest Ophthalmol Vis Sci (ARVO Suppl) 1996;37:S983.

    Google Scholar 

  74. Gordon-Thomson C, de Iongh RU, Hales AM, Chamberlain CG, McAvoy JW . Differential cataractogenic potency of TGF-l, TGFβ-2 and TGFβ-3 and their expression in the postnatal rat eye. Invest Ophthalmol Vis Sci 1998;39:1399–409.

    CAS  PubMed  Google Scholar 

  75. Schulz MW, Chamberlain CG, McAvoy JW . Inhibition of TGFβ-induced cataractous changes in lens explants by ocular media and α2-macroglobulin. Invest Ophthalmol Vis Sci 1996;37:1509–19.

    CAS  PubMed  Google Scholar 

  76. de Iongh RU, McAvoy JW . Spatio-temporal distribution of acidic and basic FGF indicates a role for FGF in rat lens morphogenesis. Dev Dynam 1993;198:190–202.

    Article  CAS  Google Scholar 

  77. McAvoy JW . The spatial relationship between presumptive lens and optic vesicle/cup during early eye morphogenesis in the rat. Exp Eye Res 1981;33:447–58.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Histology and Institute for Biomedical Research, University of Sydney, Sydney, Australia

    J W McAvoy, C G Chamberlain, R U de Longh, A M Hales & F J Lovicu

Authors
  1. J W McAvoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C G Chamberlain
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R U de Longh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A M Hales
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F J Lovicu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J W McAvoy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McAvoy, J., Chamberlain, C., de Longh, R. et al. Lens development. Eye 13, 425–437 (1999). https://doi.org/10.1038/eye.1999.117

Download citation

  • Issue Date: May 1999

  • DOI: https://doi.org/10.1038/eye.1999.117

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • Fibroblast growth factor
  • Induction
  • Lens development
  • Morphogenesis
  • Transcription factors
  • Transforming growth factor-beta

This article is cited by

  • Aquaporin water channels: roles beyond renal water handling

    • Frédéric H. Login
    • Lene N. Nejsum

    Nature Reviews Nephrology (2023)

  • Cellular FLICE-like inhibitory protein (cFLIP) critically maintains apoptotic resistance in human lens epithelial cells

    • Jingru Huangfu
    • Caili Hao
    • Xingjun Fan

    Cell Death & Disease (2021)

  • Glycation-mediated protein crosslinking and stiffening in mouse lenses are inhibited by carboxitin in vitro

    • Sandip K. Nandi
    • Johanna Rankenberg
    • Ram H. Nagaraj

    Glycoconjugate Journal (2021)

  • Calponin-3 deficiency augments contractile activity, plasticity, fibrogenic response and Yap/Taz transcriptional activation in lens epithelial cells and explants

    • Rupalatha Maddala
    • Maureen Mongan
    • Ponugoti Vasantha Rao

    Scientific Reports (2020)

  • Connexin43 and connexin50 channels exhibit different permeability to the second messenger inositol triphosphate

    • Virginijus Valiunas
    • Thomas W. White

    Scientific Reports (2020)

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Current issue
  • Collections
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open Access Fees and Funding
  • About the Editors
  • Journal News
  • Special Issues
  • About the Partner
  • EYE Covers
  • Contact
  • For Advertisers
  • Subscribe

Publish with us

  • For Authors & Referees
  • Language editing services
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Eye (Eye) ISSN 1476-5454 (online) ISSN 0950-222X (print)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Italy
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2025 Springer Nature Limited