Lens Induction

Abstract

Lens tissue develops from the embryonic head ectoderm through its interaction with the retinal primordium, the optic vesicle. This developmental mechanism has served as a paradigm of embryonic tissues induction. The application of modern techniques for gene manipulation and monitoring gene activities in developing embryonic tissues have revealed the two optic vesicle‐dependent mechanisms that underlie the lens induction process: local activation of the cooperative transcription factors SOX2 (SRY‐related‐HMG‐box 2) and PAX6 (paired box 6) in the head ectoderm; and elimination of the influence of the cephalic neural crest, which is otherwise inhibitory to lens development. Lens induction reciprocally influences the development of the optic vesicle and organizes the lens‐centered optic cup. The action of SOX2 and PAX6 is also common to other lens‐generating processes, including during lens regeneration from the dorsal iris in the newt eye, and lens transdifferentiation from the pituitary primordium as occurs in certain mutant embryos.

Key concepts:

  • Tissue induction is the process of deriving new cell types from a tissue through interaction with another tissue.

  • Transcription factors are proteins that regulate gene transcription by binding to the gene regulatory regions of DNA.

  • Signalling molecules, which are often proteins, are secreted from a group of cells, bound by receptors on another group of cells, and cause changes in the cells that bind the molecules.

Keywords: lens; head ectoderm; optic vesicle; Sox2; Pax6; crystallin

Figure 1.

Crystallin expression in the lens. A histological section through the eye of a 3‐day‐old chicken embryo stained with anti‐δ‐crystallin antibodies. Lens epithelium (LE) and lens fibres (LF) are indicated.

Figure 2.

Schematic representation of experiments utilizing ablation of the retina rudiment (optic vesicle) as initially described by Spemann .

Figure 3.

The temporal order of the expression (broken arrows) and activity (solid arrows) of transcription factors active during the early stages of lens development. Histological sections of chicken embryo at the developmental stages indicated at the top of each panel are used as a template for illustrations, but the scheme also applies to a wide range of vertebrate species. Crystallin expression in the chicken lens is also indicated as a reference.

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References

Ashery‐Padan R, Marquardt T, Zhou X and Gruss P (2000) Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye. Genes & Development 14: 2701–2711.

Bailey AP, Bhattacharyya S, Bronner‐Fraser M and Streit A (2006) Lens specification is the ground state of all sensory placodes, from which FGF promotes olfactory identity. Developmental Cell 11: 505–517.

Faber SC, Dimanlig P, Makarenkova HP et al. (2001) Fgf receptor signaling plays a role in lens induction. Development 128: 4425–4438.

Fujiwara M, Uchida T, Osumi‐Yamashita N and Eto K (1994) Uchida rat (rSey): a new mutant rat with craniofacial abnormalities resembling those of the mouse Sey mutant. Differentiation 57: 31–38.

Furuta Y and Hogan BL (1998) BMP4 is essential for lens induction in the mouse embryo. Genes & Development 12: 3764–3775.

Grainger RM, Herry JJ and Henderson RA (1988) Reinvestigation of the role of the optic vesicle in embryonic lens induction. Development 102: 517–526.

Grindley JC, Davidson DR and Hill RE (1995) The role of Pax‐6 in eye and nasal development. Development 121: 1433–1442.

Hayashi T, Mizuno N, Takada R, Takada S and Kondoh H (2006) Determinative role of Wnt signals in dorsal iris‐derived lens regeneration in newt eye. Mechanical Development 123: 793–800.

Hayashi T, Mizuno N, Ueda Y, Okamoto M and Kondoh H (2004) FGF2 triggers iris‐derived lens regeneration in newt eye. Mechanical Development 121: 519–526.

Henry JJ and Grainger RM (1987) Inductive interactions in the spatial and temporal restriction of lens‐forming potential in embryonic ectoderm of Xenopus laevis. Developmental Biology 124: 200–214.

Hill RE, Favor J, Hogan BL et al. (1991) Mouse small eye results from mutations in a paired‐like homeobox‐containing gene. Nature 354: 522–525.

Hogan BL, Horsburgh G, Cohen J et al. (1986) Small eyes (Sey): a homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse. Journal of Embryology and Experimental Morphology 97: 95–110.

Hyer J, Kuhlman J, Afif E and Mikawa T (2003) Optic cup morphogenesis requires pre‐lens ectoderm but not lens differentiation. Developmental Biology 259: 351–363.

Kamachi Y, Iwafuchi M, Okuda Y et al. (2009) Evolution of non‐coding regulatory sequences involved in the developmental process: reflection of differential employment of paralogous genes as highlighted by Sox2 and group B1 Sox genes. Proceedings of the Japan Academy. Series B, Physical and Biological Sciences 85: 55–68.

Kamachi Y, Uchikawa M, Collignon J, Lovell‐Badge R and Kondoh H (1998) Involvement of Sox1, 2 and 3 in the early and subsequent molecular events of lens induction. Development 125: 2521–2532.

Kamachi Y, Uchikawa M, Tanouchi A, Sekido R and Kondoh H (2001) Pax6 and SOX2 form a co‐DNA‐binding partner complex that regulates initiation of lens development. Genes & Development 15: 1272–1286.

Kondoh H and Kamachi Y (2010) SOX‐partner code for cell specification: regulatory target selection and underlying molecular mechanisms. International Journal of Biochemistry & Cell Biology 42: 391–399.

Kondoh H, Uchikawa M, Yoda H et al. (2000) Zebrafish mutations in Gli‐mediated hedgehog signaling lead to lens transdifferentiation from the adenohypophysis anlage. Mechanical Development 96: 165–174.

Lewis W (1904) Experimental studies on the development of the eye in amphibia. I. On the origin of the lens Rana palustris. American Journal of Anatomy 3: 505–536.

Li HS, Yang JM, Jacobson RD, Pasko D and Sundin O (1994) Pax‐6 is first expressed in a region of ectoderm anterior to the early neural plate: implications for stepwise determination of the lens. Developmental Biology 162: 181–194.

Medina‐Martinez O and Jamrich M (2007) Foxe view of lens development and disease. Development 134: 1455–1463.

Medina‐Martinez O, Shah R and Jamrich M (2009) Pitx3 controls multiple aspects of lens development. Developmental Dynamics 238: 2193–2201.

Nishiguchi S, Wood H, Kondoh H, Lovell‐Badge R and Episkopou V (1998) Sox1 directly regulates the gamma‐crystallin genes and is essential for lens development in mice. Genes& Development 12: 776–781.

Ogino H, Fisher M and Grainger RM (2008) Convergence of a head‐field selector Otx2 and Notch signaling: a mechanism for lens specification. Development 135: 249–258.

Ogino H and Yasuda K (1998) Induction of lens differentiation by activation of a bZIP transcription factor, L‐Maf. Science 280: 115–118.

Rajaram N and Kerppola TK (2004) Synergistic transcription activation by Maf and Sox and their subnuclear localization are disrupted by a mutation in Maf that causes cataract. Molecular and Cellular Biology 24: 5694–5709.

Shaham O, Smith AN, Robinson ML et al. (2009) Pax6 is essential for lens fiber cell differentiation. Development 136: 2567–2578.

Smith AN, Miller LA, Radice G, Ashery‐Padan R and Lang RA (2009) Stage‐dependent modes of Pax6‐Sox2 epistasis regulate lens development and eye morphogenesis. Development 136: 2977–2985.

Spemann H (1901) Ueber Correlationen in der Entwickelung des Auges. Verhandeligen der Anatomisches Geselschaft 15: 61–79.

Stump RJ, Ang S, Chen Y et al. (2003) A role for Wnt/beta‐catenin signaling in lens epithelial differentiation. Developmental Biology 259: 48–61.

Sullivan CH, Braunstein L, Hazard‐Leonards RM et al. (2004) A re‐examination of lens induction in chicken embryos: in vitro studies of early tissue interactions. International Journal of Developmental Biology 48: 771–782.

Takeuchi T, Kudo T, Ogata K et al. (2009) Neither MafA/L‐Maf nor MafB is essential for lens development in mice. Genes and Cells 14: 941–947.

Wawersik S, Purcell P, Rauchman M et al. (1999) BMP7 acts in murine lens placode development. Developmental Biology 207: 176–188.

Wigle JT, Chowdhury K, Gruss P and Oliver G (1999) Prox1 function is crucial for mouse lens‐fibre elongation. Nature Genetics 21: 318–322.

Yoshimoto A, Saigou Y, Higashi Y and Kondoh H (2005) Regulation of ocular lens development by Smad‐interacting protein 1 involving Foxe3 activation. Development 132: 4437–4448.

Zhang Y, Burgess D, Overbeek PA and Govindarajan V (2008) Dominant inhibition of lens placode formation in mice. Developmental Biology 323: 53–63.

Further Reading

Grainger RM (1992) Embryonic lens induction: shedding light on vertebrate tissue determination. Trends in Genetics 8: 349–355.

Hamburger V (1988) The Heritage of Experimental Embryology: Hans Spemann and the Organizer. New York: Oxford University Press.

Hayashi T, Mizuno N and Kondoh H (2008) Determinative roles of FGF and Wnt signals in iris‐derived lens regeneration in newt eye. Development Growth and Differentiation 50: 279–287.

Kondoh H (2008) Shedding light on developmental gene regulation through the lens. Development Growth and Differentiation 50(suppl. 1): S57–S69.

Kondoh H, Uchikawa M and Kamachi Y (2004) Interplay of Pax6 and SOX2 in lens development as a paradigm of genetic switch mechanisms for cell differentiation. International Journal of Developmental Biology 48: 819–827.

Okada TS (1991) Transdifferentiation. New York: Oxford University Press.

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How to Cite close
Kondoh, Hisato(Apr 2010) Lens Induction. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001142.pub2]