Wigle J T, Chowdhury K, Gruss P, Oliver G
Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Nat Genet. 1999 Mar;21(3):318-22. doi: 10.1038/6844.
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 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.
尽管在控制眼睛形成早期阶段的基因方面已经有了一些见解，但对于晶状体纤维的分化和伸长却知之甚少。Prox1同源盒基因的表达模式表明它在包括晶状体在内的多种胚胎组织中发挥作用。为了分析Prox1在哺乳动物发育过程中的需求，我们使小鼠体内的该基因座失活。纯合Prox1基因敲除小鼠在妊娠中期因多种发育缺陷而死亡；在此我们描述其对晶状体发育的具体影响。Prox1失活导致细胞增殖异常、细胞周期抑制剂Cdkn1b（也称为p27KIP1）和Cdkn1c（也称为p57KIP2）的表达下调、E-钙黏蛋白的错误表达以及不适当的细胞凋亡。因此，突变的晶状体细胞无法正常极化和伸长，导致晶状体中空。我们的数据提供了证据，表明在晶状体发育过程中，终末纤维分化和伸长的进程依赖于Prox1的活性。
