Prox1 function is crucial for mouse lens-fibre elongation

Jeffrey T. Wigle, Kamal Chowdhury, Peter Gruss, Guillermo Oliver*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

338 Scopus citations

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 lens. 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 p27(KIP1)) and Cdkn1c(also known as p57(KIP2)), 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.

Original languageEnglish (US)
Pages (from-to)318-322
Number of pages5
JournalNature Genetics
Volume21
Issue number3
DOIs
StatePublished - Mar 1999

ASJC Scopus subject areas

  • Genetics

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