Zebrafish prickle, a modulator of noncanonical Wnt/Fz signaling, regulates gastrulation movements
Zebrafish prickle, a modulator of noncanonical Wnt/Fz signaling, regulates gastrulation movements
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斑马鱼皮刺是非典型 Wnt/Fz 信号传导的调节器，可调控胃形成运动
DOI：
10.1016/s0960-9822(03)00240-9
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发表时间：
2003-04-15
期刊：
影响因子：
9.2
通讯作者：
Moon, RT
中科院分区：
文献类型：
--
作者：
Veeman, MT;Slusarski, DC;Moon, RT
除了经典的Wnt/β-连环蛋白信号通路之外，还描述了至少两种非经典的Wnt/Fz通路：果蝇中的平面细胞极性（PCP）通路[1]和脊椎动物胚胎中的Wnt/钙通路[2]。最近的工作表明，脊椎动物途径同源的PCP途径的作用，以调节原肠形成的收敛伸展运动[3-7]。为了进一步验证这一假设，我们鉴定了果蝇PCP基因prickle（pk）[8]的两种斑马鱼同源物，这两种同源物在原肠胚形成期间均显示出离散且动态的表达模式。pk 1函数的增益和损失都会导致收敛延拓的缺陷。PK 1定位于细胞质和细胞膜，其正常定位部分依赖于其C-末端异戊烯基序。在细胞膜上，Pk 1经常不对称地定位在细胞周围，并且可以与信号分子Dishevelled（Dsh）共定位。在过表达测定中，Pk 1能够激活AP-1介导的转录并抑制Wnt/β-连环蛋白信号传导的激活。与非典型钙离子类似[9，10]，Pk 1的过表达增加了斑马鱼囊胚中钙瞬变的频率。我们的研究结果支持脊椎动物PCP途径调节原肠胚形成运动的想法，并表明PCP和Wnt/钙途径之间存在重叠。
In addition to the canonical Wnt/beta-catenin signaling pathway, at least two noncanonical Wnt/Fz pathways have been described: the planar cell polarity (PCP) pathway in Drosophila [1] and the Wnt/calcium pathway in vertebrate embryos [2]. Recent work suggests that a vertebrate pathway homologous to the PCP pathway acts to regulate the convergent extension movements of gastrulation [3-7]. To further test this hypothesis, we have identified two zebrafish homologs of the Drosophila PCP gene prickle (pk) [8], both of which show discrete and dynamic expression patterns during gastrulation. Both gain and loss of pk1 function cause defects in convergent extension. Pk1 localizes to both the cytoplasm and the cell membrane, and its normal localization is partially dependent on its C-terminal prenylation motif. At the cell membrane, Pk1 is frequently localized asymmetrically around the cell and can colocalize with the signaling molecule Dishevelled (Dsh). In overexpression assays, Pk1 is able to activate AP-1-mediated transcription and inhibit activation of Wnt/beta-catenin signaling. Like noncanonical Writs [9, 10], overexpression of Pk1 increases the frequency of calcium transients in zebrafish blastulae. Our results support the idea that a vertebrate PCP pathway regulates gastrulation movements and suggest that there is overlap between the PCP and Wnt/calcium pathways.