Sackler Faculty of Medicine, Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Prog Retin Eye Res. 2012 Sep;31(5):351-76. doi: 10.1016/j.preteyeres.2012.04.002. Epub 2012 May 3.
Eye development has been a paradigm for the study of organogenesis, from the demonstration of lens induction through epithelial tissue morphogenesis, to neuronal specification and differentiation. The transcription factor Pax6 has been shown to play a key role in each of these processes. Pax6 is required for initiation of developmental pathways, patterning of epithelial tissues, activation of tissue-specific genes and interaction with other regulatory pathways. Herein we examine the data accumulated over the last few decades from extensive analyses of biochemical modules and genetic manipulation of the Pax6 gene. Specifically, we describe the regulation of Pax6's expression pattern, the protein's DNA-binding properties, and its specific roles and mechanisms of action at all stages of lens and retinal development. Pax6 functions at multiple levels to integrate extracellular information and execute cell-intrinsic differentiation programs that culminate in the specification and differentiation of a distinct ocular lineage.
眼睛发育一直是器官发生研究的范例,从通过上皮组织形态发生证明晶状体诱导,到神经元特化和分化。转录因子 Pax6 已被证明在这些过程中的每一个都发挥着关键作用。Pax6 对于发育途径的启动、上皮组织的模式形成、组织特异性基因的激活以及与其他调节途径的相互作用都是必需的。在这里,我们检查了过去几十年中通过对 Pax6 基因的生化模块的广泛分析和遗传操作积累的数据。具体来说,我们描述了 Pax6 表达模式的调节、该蛋白的 DNA 结合特性,以及它在晶状体和视网膜发育的所有阶段的特定作用和作用机制。Pax6 在多个层面上发挥作用,整合细胞外信息并执行细胞内在的分化程序,最终导致特定的眼系分化。