Multiple steps in cell differentiaion : the case of lens development

头部外胚层需要Pax6的活性才能对视泡的诱导信号(S)有反应。在随后的晶状体发育过程中，Pax6的表达保持不变。当纤维和上皮细胞分化时，Pax6在上皮室中的表达仍然很高，但在纤维室中的表达减少，这表明Pax6在晶状体上皮细胞中的第二个作用是维持基本状态。鉴定参与晶状体诱导后阶段的转录因子的方法是鉴定那些开启晶体蛋白基因的转录因子。在晶体蛋白基因中，鸡β-晶体蛋白的表达似乎是最早的，从晶状体胎盘的晚期开始。从鸡中克隆了一组与晶状体特异的基因内增强子中间结合的转录因子，并发现它们是B组Sox蛋白Sox1、Sox2和Sox3。视泡与头部外胚层紧密接触后，Sox2和SOX3在头部外胚层表达，与视泡接触的区域和形成晶状体胎盘的区域完全对应。然后，启动了反映Sox2/3蛋白作用的Delta-Crystal allin基因的表达。SOX1的表达开始较晚，并成为晶状体发育后期的主要SOX蛋白。在小鼠晶状体中，Sox2的表达在晶状体诱导过程中被激活，但随着Sox1的激活而很快被关闭。SOX1缺陷小鼠是通过定向破坏该基因而产生的。在纯合子中，在Sox2被关闭的阶段，晶状体发育受阻，γ-晶状体蛋白表达减少，证实了Sox蛋白在晶状体发育和晶状体蛋白基因激活中的重要功能。

Pax6 activity is required for the head ectoderm to have responsiveness to the inductive signal(s) of the optic vesicle. Pax6 expression is maintained in the following lens development. When the fibers and epithelia differentiate, Pax6 expression remains high in the epithelial compartment but decreases in the fiber compartment, suggesting its second role in the lens epithelium in maintaining the rudimentary state.An approach to identifying transcription factors involved in the stages following lens induction is to identify those which turn on crystallin genes. Among the crystallin genes, chicken delta-crystallin seems to be the earliest in its expression, starting from the late lens placode stage. A group of related transcription factors which bind to the middle of the lens-specific intragenic enhancer and are essential for the delta-crystallin gene expression were cloned from the chicken, and found to be Group B Sox proteins, Sox1, 2 and 3. Immediately following the stage of tight contact of the optic vesicle to the head ectoderm, Sox2 and Sox3 are expressed in regions of the head ectoderm which correspond exactly to those contacted by the optic vesicle and to those giving rise to the lens placode. Then, delta-crystallin gene expression is initiated reflecting the action of the Sox2/3 proteins. Sox1 expression starts slightly later, and becomes the major Sox protein in the later lens development. In the mouse lens also, Sox2 expression is activated during lens induction, but is soon turned off as Sox1 is activated. Sox1 deficient mice were produced by targeted disruption of the gene. In the homozygotes, lens development is arrested and gamma-crystallin expression is diminished at the stage at which Sox2 is turned off, confirming the essential function of Sox proteins in lens development and in crystallin gene activation.