Niimi T, Seimiya M, Kloter U, Flister S, Gehring W J
Biozentrum University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Development. 1999 May;126(10):2253-60. doi: 10.1242/dev.126.10.2253.
The Pax-6 gene encodes a transcription factor with two DNA-binding domains, a paired and a homeodomain, and is expressed during eye morphogenesis and development of the nervous system. Pax-6 homologs have been isolated from a wide variety of organisms ranging from flatworms to humans. Since loss-of-function mutants in insects and mammals lead to an eyeless phenotype and Pax-6 orthologs from distantly related species are capable of inducing ectopic eyes in Drosophila, we have proposed that Pax-6 is a universal master control gene for eye morphogenesis. To determine the extent of evolutionary conservation of the eye morphogenetic pathway, we have begun to identify subordinate target genes of Pax-6. Previously we have shown that expression of two genes, sine oculis (so) and eyes absent (eya), is induced by eyeless (ey), the Pax-6 homolog of Drosophila. Here we present evidence from ectopic expression studies in transgenic flies, from transcription activation studies in yeast, and from gel shift assays in vitro that the EY protein activates transcription of sine oculis by direct interaction with an eye-specific enhancer in the long intron of the so gene.
Pax-6基因编码一种具有两个DNA结合结构域（一个配对结构域和一个同源结构域）的转录因子，在眼睛形态发生和神经系统发育过程中表达。已从从扁虫到人类等多种生物体中分离出Pax-6同源物。由于昆虫和哺乳动物中的功能丧失突变体导致无眼表型，且远缘物种的Pax-6直系同源物能够在果蝇中诱导异位眼的形成，我们提出Pax-6是眼睛形态发生的通用主控基因。为了确定眼睛形态发生途径的进化保守程度，我们已开始鉴定Pax-6的下游靶基因。此前我们已表明，果蝇的Pax-6同源物无眼（ey）可诱导两个基因——眼缺失（so）和无眼（eya）的表达。在此，我们提供了来自转基因果蝇异位表达研究、酵母转录激活研究以及体外凝胶迁移试验的证据，证明EY蛋白通过与so基因长内含子中的眼睛特异性增强子直接相互作用来激活眼缺失的转录。
