Multiple steps in cell differentiaion : the case of lens development

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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.