Kim Jun-Dae, Chun Hang-Suk, Kim Seok-Hyung, Kim Hyung-Seok, Kim Young-Seop, Kim Myoung-Jin, Shin Jimann, Rhee Myungchull, Yeo Sang-Yeob, Huh Tae-Lin
Kyungpook National University, Buk-gu, Daegu, Republic of Korea.
Biochem Biophys Res Commun. 2009 Apr 17;381(4):717-21. doi: 10.1016/j.bbrc.2009.02.135. Epub 2009 Mar 1.
During normal forebrain development in vertebrates, rostral neural tissue must be protected from Wnt signals via the actions of locally expressed Wnt antagonistic factors. In zebrafish zygotic oep (Zoep) mutants, forebrain structure is severely disrupted with reduced expression of the Wnt antagonists secreted frizzled related protein1 and dickkopf1. To analyze the temporal effects of Wnt antagonism on forebrain development, we generated transgenic zebrafish that overexpressed the dominant negative form of frizzled8a (DNfz8a) in wild-type and Zoep mutants under the control of a heat-inducible promoter. This model allowed for assessment of the dynamics of Wnt antagonistic signaling during forebrain development. Our results demonstrated that overexpression of DNfz8a in Zoep embryos between 7 and 16hpf increased putative forebrain region demarcated by anf and distal-less2 expressions. These results suggest that normal forebrain development requires continual Wnt antagonism from the early gastrula to the mid-somitogenesis stage.
在脊椎动物前脑的正常发育过程中，头部神经组织必须通过局部表达的Wnt拮抗因子的作用来免受Wnt信号的影响。在斑马鱼合子oep（Zoep）突变体中，前脑结构严重受损，Wnt拮抗剂分泌型卷曲相关蛋白1和dickkopf1的表达降低。为了分析Wnt拮抗作用对前脑发育的时间效应，我们构建了转基因斑马鱼，其在热诱导启动子的控制下在野生型和Zoep突变体中过表达卷曲蛋白8a（DNfz8a）的显性负性形式。该模型有助于评估前脑发育过程中Wnt拮抗信号的动态变化。我们的结果表明，在7至16小时胚胎发育期的Zoep胚胎中过表达DNfz8a会增加由anf和远端缺失2表达所界定的假定前脑区域。这些结果表明，正常的前脑发育需要从早期原肠胚到中体节形成阶段持续的Wnt拮抗作用。
