Multiple steps in cell differentiaion : the case of lens development

Pax 6活性是头部外胚层对视泡的诱导信号具有响应性所必需的。Pax 6表达在随后的透镜发育中得以维持。当纤维和上皮细胞分化，Pax 6的表达仍然很高的上皮室，但在纤维室减少，这表明其第二个作用在透镜上皮细胞在维持的基本状态。一种方法来确定转录因子参与的阶段后，透镜诱导是确定那些打开晶体蛋白基因。在晶体蛋白基因中，鸡δ-晶体蛋白似乎是其表达最早的，从透镜基板阶段晚期开始。从鸡中克隆了一组与晶状体特异性基因内增强子中部结合并对δ-晶状体蛋白基因表达至关重要的相关转录因子，并发现它们是B族Sox蛋白，Sox 1、2和3。紧随视泡与头部外胚层紧密接触的阶段之后，Sox 2和Sox 3在头部外胚层的区域中表达，所述区域恰好对应于与视泡接触的区域和产生透镜基板的区域。然后，δ-晶状体蛋白基因表达开始，反映Sox 2/3蛋白的作用。Sox 1的表达开始稍晚，并成为透镜发育后期的主要Sox蛋白。同样，在小鼠透镜中，Sox 2表达在透镜诱导期间被激活，但是随着Sox 1被激活而很快被关闭。通过靶向破坏该基因产生Sox 1缺陷小鼠。在纯合子中，透镜发育被阻止，并且在Sox 2关闭的阶段γ-晶状体蛋白表达减少，证实了Sox蛋白在透镜发育和晶状体蛋白基因激活中的基本功能。

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.