Peek R, McAvoy J W, Lubsen N H, Schoenmakers J G
Department of Molecular Biology, University of Nijmegen, The Netherlands.
Dev Biol. 1992 Jul;152(1):152-60. doi: 10.1016/0012-1606(92)90165-d.
Explanted rat lens epithelial cells differentiate synchronously in vitro to lens fiber cells in the presence of basic fibroblast growth factor (bFGF). We have monitored the expression of the three rat crystallin gene families, the alpha-, beta-, and gamma-crystallin genes, during this process. The expression of these gene families is sequentially activated, first the alpha-crystallin genes at Day 1, then the beta-crystallin genes at Day 3, and finally the gamma-crystallin genes at Day 8. The steady state levels of alpha- and beta-crystallin mRNA are not affected by incubation with actinomycin D, suggesting that these mRNAs are stable. Nevertheless, all crystallin mRNAs disappear from the differentiated explants between Days 10 and 11, a process signaled by bFGF. At this time a novel abundant mRNA appears. Cloning and sequencing showed that this mRNA encoded aldose reductase. Our results suggest a novel model for the regulation of crystallin synthesis during lens cell differentiation: a gene pulse delivers a certain amount of stable mRNA, this mRNA is removed at a later stage of differentiation by a stage-specific breakdown mechanism. Each of these regulatory steps requires a signal from bFGF.
在碱性成纤维细胞生长因子（bFGF）存在的情况下，移植的大鼠晶状体上皮细胞在体外可同步分化为晶状体纤维细胞。在此过程中，我们监测了大鼠三个晶状体蛋白基因家族（α-、β-和γ-晶状体蛋白基因）的表达情况。这些基因家族的表达是依次被激活的，首先是在第1天激活α-晶状体蛋白基因，然后在第3天激活β-晶状体蛋白基因，最后在第8天激活γ-晶状体蛋白基因。α-和β-晶状体蛋白mRNA的稳态水平不受放线菌素D孵育的影响，这表明这些mRNA是稳定的。然而，所有晶状体蛋白mRNA在第10天至第11天之间从分化的外植体中消失，这一过程由bFGF发出信号。此时出现了一种新的丰富mRNA。克隆和测序表明，这种mRNA编码醛糖还原酶。我们的结果提示了一种晶状体细胞分化过程中晶状体蛋白合成调控的新模型：基因脉冲传递一定量的稳定mRNA，这种mRNA在分化后期通过阶段特异性降解机制被清除。这些调控步骤中的每一步都需要来自bFGF的信号。
