Prickle 1 regulates cell movements during gastrulation and neuronal migration in zebrafish
Prickle 1 regulates cell movements during gastrulation and neuronal migration in zebrafish
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DOI：
10.1242/dev.00567
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发表时间：
2003-09-01
期刊：
影响因子：
4.6
通讯作者：
Tada, M
中科院分区：
文献类型：
--
作者：
Carreira-Barbosa, F;Concha, ML;Tada, M
在脊椎动物原肠胚形成过程中，中胚层和外胚层细胞经历会聚延伸，这一过程以突出的细胞重排为特征，其中极化细胞沿中外侧轴插入，导致前后轴伸长。近年来，人们发现与果蝇平面细胞极性（PCP）通路相关的非规范Wnt/ frizzed (Fz)/ disheveled （Dsh）信号通路调节脊椎动物原肠胚形成过程中的趋同延伸。在这里，我们分离并功能表征了斑马鱼的刺状果蝇（pk）同源基因，该基因与PCP的调节有关。斑马鱼pk1在母体和移动的中胚层前体中表达。形态学寡核苷酸对Pk1功能的破坏导致趋同延伸运动的缺陷，增强了silberblick (slb)1wnt11和pipe - tail (Ppt)/wnt5表型，抑制了Wnt11挽救slb表型的能力。Pk1的功能获得也抑制趋同伸展运动并增强s1b表型，这很可能是由于Pk1能够通过下调Dsh蛋白水平来阻断fz7依赖性Dsh的膜定位。此外，我们发现pk1与三叶虫/斜视基因相互作用，介导颅运动神经元的尾侧定向迁移和收敛延伸。这些结果表明，在斑马鱼原肠胚形成过程中，Pk1部分通过与非规范的Wnt11/Wnt5途径相互作用来调节趋同扩展细胞运动，但不太可能仅仅是该途径的线性组成部分。此外，Pk1与Tri相互作用介导支运动神经元的后向迁移，可能独立于非规范的Wnt通路。
During vertebrate gastrulation, mesodermal and ectodermal cells undergo convergent extension, a process characterised by prominent cellular rearrangements in which polarised cells intercalate along the medio-lateral axis leading to elongation of the antero-posterior axis. Recently, it has become evident that a noncanonical Wnt/Frizzled (Fz)/Dishevelled (Dsh) signalling pathway, which is related to the planar-cell-polarity (PCP) pathway in flies, regulates convergent extension during vertebrate gastrulation. Here we isolate and functionally characterise a zebrafish homologue of Drosophila prickle (pk), a gene that is implicated in the regulation of PCP. Zebrafish pk1 is expressed maternally and in moving mesodermal precursors. Abrogation of Pk1 function by morpholino oligonucleotides leads to defective convergent extension movements, enhances the silberblick (slb)1wnt11 and pipetail (Ppt)/wnt5 phenotypes and suppresses the ability of Wnt11 to rescue the slb phenotype. Gain-of-function of Pk1 also inhibits convergent extension movements and enhances the s1b phenotype, most likely caused by the ability of Pk1 to block the Fz7-dependent membrane localisation of Dsh by downregulating levels of Dsh protein. Furthermore, we show that pk1 interacts genetically with trilobite (tri)/strabismus to mediate the caudally directed migration of cranial motor neurons and convergent extension. These results indicate that, during zebrafish gastrulation Pk1 acts, in part, through interaction with the noncanonical Wnt11/Wnt5 pathway to regulate convergent extension cell movements, but is unlikely to simply be a linear component of this pathway. In addition, Pk1 interacts with Tri to mediate posterior migration of branchiomotor neurons, probably independent of the noncanonical Wnt pathway.