Prox1 function is crucial for mouse lens-fibre elongation

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 far 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 an lens development Prox1 inactivation causes abnormal cellular proliferation, downregulated expression of the cell-cycle inhibitors Cdkn Ib (also known as p27(KIP1)) and Cdkn1b (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.