Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye
Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye
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DOI：
10.1101/gad.184000
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发表时间：
2000-11-01
影响因子：
10.5
通讯作者：
Gruss, P
中科院分区：
文献类型：
--
作者：
Ashery-Padan, R;Marquardt, T;Gruss, P
Pax 6转录因子在脊椎动物和无脊椎动物的眼发育中起关键作用。人和小鼠Pax 6无效突变的纯合性导致视泡发育停滞和不能启动透镜形成。这种表型模糊了对Pax 6在这些组织成分中以及在以后的发育阶段中的自主功能的理解。我们采用Cre/loxP方法在眼表面外胚层中特异性地表达Pax 6，同时伴随透镜诱导。虽然透镜诱导发生在突变体中，如表面外胚层中的Sore上调所示，但透镜的进一步发育被阻止。因此，发现Pax 6活性在特定的外胚层中对于透镜基板形成是必需的。此外，这种突变模型使我们第一次能够在体内解决在没有早期透镜结构的情况下完全正常视网膜的发育。值得注意的是，在没有透镜的情况下，在单个视泡中发育了几个独立的、完全分化的神经视网膜，这表明发育中的透镜对于指导神经视网膜的分化不是必需的，而是对于眼睛中单个视网膜的正确放置是必需的。
The Pax6 transcription factor plays a key role in ocular development of vertebrates and invertebrates. Homozygosity of the Pax6 null mutation in human and mice results in arrest of optic vesicle development and failure to initiate lens formation. This phenotype obscures the understanding of autonomous function of Pax6 in these tissue components and during later developmental stages. We employed the Cre/loxP approach to inactivate Pax6 specifically in the eye surface ectoderm concomitantly with lens induction. Although lens induction occurred in the mutant, as indicated by Sore up-regulation in the surface ectoderm, further development of the lens was arrested. Hence, Pax6 activity was found to be essential in the specified ectoderm for lens placode formation. Furthermore, this mutant model allowed us for the first time to address in vivo the development of a completely normal retina in the absence of early lens structures. Remarkably, several independent, fully differentiated neuroretinas developed in a single optic vesicle in the absence of a lens, demonstrating that the developing lens is not necessary to instruct the differentiation of the neuroretina but is, rather, required for the correct placement of a single retina in the eye.