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Prox1 function is crucial for mouse lens-fibre elongation

Nature Genetics volume 21, pages 318–322 (1999)Cite this article

Abstract

Although insights have emerged regarding genes controlling the early stages of eye formation, little is known about lens-fibre differentiation and elongation. The expression pattern of the Prox1 homeobox gene suggests it has a role in a variety of embryonic tissues, including lens1. To analyse the requirement for Prox1 during mammalian development, we inactivated the locus in mice. Homozygous Prox1-null mice die at mid-gestation from multiple developmental defects; here we describe the specific effect on lens development. Prox1 inactivation causes abnormal cellular proliferation, downregulated expression of the cell-cycle inhibitors Cdkn1b (also known as p27KIP1) and Cdkn1c (also known as p57KIP2), misexpression of E-cadherin and inappropriate apoptosis. Consequently, mutant lens cells fail to polarize and elongate properly, resulting in a hollow lens. Our data provide evidence that the progression of terminal fibre differentiation and elongation is dependent on Prox1 activity during lens development.

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Figure 1: Targeted disruption of Prox1.
Figure 2: Lens-fibre elongation is affected in Prox1–/– mice.
Figure 3: Altered cellular proliferation in Prox1–/– lens.
Figure 4: Prox1 regulates Cdkn1b and Cdkn1c expression in the lens.
Figure 5: Analysis of crystallin gene expression.
Figure 6: E-cadherin is uniformly expressed in Prox1 mutant lenses.

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Acknowledgements

We thank M. Torres, S. Geisendorf, S. Mahsur and C. Nagy for help with the initial steps of the knockout; H. Brinkman for technical assistance; R. Lovell-Badge for Sox1 antibody; R. Quinlan for CP49 and filensin antibodies; S.J. Elledge for communicating results before publication; P. Overbeek for suggestions, comments and the Crya1 and Cdkn1c probes; an anonymous referee for helpful comments; and J. Cleveland, G. Grosveld and C. Wright for critical reading of the manuscript. This work was partially supported by National Institutes of Health grant GM58462 (G.O.), by Cancer Center Support (CORE) grant CA 21765 and by the American Lebanese and Syrian Associated Charities (ALSAC) of St. Jude Children's Research Hospital.

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Authors and Affiliations

  1. Department of Genetics, St. Jude Children's Research Hospital, 332 North Lauderdale St, Memphis, 38105, Tennessee, USA

    Jeffrey T. Wigle & Guillermo Oliver

  2. Max Planck Institute for Biophysical Chemistry, Am Fassberg, Goettingen, 37077, Germany

    Kamal Chowdhury & Peter Gruss

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  1. Jeffrey T. Wigle
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  2. Kamal Chowdhury
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  4. Guillermo Oliver
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Correspondence to Guillermo Oliver.

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Wigle, J., Chowdhury, K., Gruss, P. et al. Prox1 function is crucial for mouse lens-fibre elongation. Nat Genet 21, 318–322 (1999). https://doi.org/10.1038/6844

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