Noncanonical Wnt-4 signaling and EAF2 are required for eye development in Xenopus laevis

Noncanonical Wnt-4 signaling and EAF2 are required for eye development in Xenopus laevis
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DOI:
10.1038/sj.emboj.7600603
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发表时间:
2005-03-23
期刊:
影响因子:
11.4
通讯作者:
Kühl, M
Kühl, M
中科院分区:
生物学1区
文献类型:
--
作者:
Maurus, D;Héligon, C;Kühl, M

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Wnt-4在发育中的神经和肾组织中表达,并且是小鼠和非洲爪蟾中肾小管发生所需的。Wnt-4在神经细胞分化中的作用尚不清楚。在这里,我们证明,Wnt-4是非洲爪蟾眼睛发育所需的。Wnt-4的这种作用依赖于β-连环蛋白非依赖性非经典Wnt信号通路的激活。此外,我们报告的EAF 2,ELL介导的RNA聚合酶II延伸因子复合物的组成部分,作为Wnt-4信号的靶基因的鉴定。EAF 2在眼内特异性表达,EAF 2的表达依赖于Wnt-4的功能。EAF 2功能的丧失导致眼睛丧失,并且Wnt-4功能的丧失可以通过EAF 2来挽救。在神经化的动物帽中,EAF 2具有调节眼睛特异性转录因子Rx表达的RNA聚合酶II延伸因子的特性。这些数据为我们对眼睛发育的理解增加了新的复杂性,并进一步证明了非经典Wnt途径在器官发育中的重要性。
Wnt-4 is expressed in developing neural and renal tissue and is required for renal tubulogenesis in mouse and Xenopus. The function of Wnt-4 in neural differentiation is unknown so far. Here we demonstrate that Wnt-4 is required for eye development in Xenopus laevis. This effect of Wnt-4 depends on the activation of a beta-catenin-independent, noncanonical Wnt signaling pathway. Furthermore, we report the identification of EAF2, a component of the ELL-mediated RNA polymerase II elongation factor complex, as a target gene of Wnt-4 signaling. EAF2 is specifically expressed in the eye and EAF2 expression was dependent on Wnt-4 function. Loss of EAF2 function results in loss of eyes and loss of Wnt-4 function could be rescued by EAF2. In neuralized animal caps, EAF2 has properties characteristic for an RNA polymerase II elongation factor regulating the expression of the eye-specific transcription factor Rx. These data add a new layer of complexity to our understanding of eye development and give further evidence for the importance of noncanonical Wnt pathways in organ development.