Jessen Jason R, Topczewski Jacek, Bingham Stephanie, Sepich Diane S, Marlow Florence, Chandrasekhar Anand, Solnica-Krezel Lilianna
Department of Biological Sciences, Vanderbilt University, VU Station B 351634, Nashville, TN 37235, USA.
Nat Cell Biol. 2002 Aug;4(8):610-5. doi: 10.1038/ncb828.
Embryonic morphogenesis is driven by a suite of cell behaviours, including coordinated shape changes, cellular rearrangements and individual cell migrations, whose molecular determinants are largely unknown. In the zebrafish, Dani rerio, trilobite mutant embryos have defects in gastrulation movements and posterior migration of hindbrain neurons. Here, we have used positional cloning to demonstrate that trilobite mutations disrupt the transmembrane protein Strabismus (Stbm)/Van Gogh (Vang), previously associated with planar cell polarity (PCP) in Drosophila melanogaster, and PCP and canonical Wnt/beta-catenin signalling in vertebrates. Our genetic and molecular analyses argue that during gastrulation, trilobite interacts with the PCP pathway without affecting canonical Wnt signalling. Furthermore, trilobite may regulate neuronal migration independently of PCP molecules. We show that trilobite mediates polarization of distinct movement behaviours. During gastrulation convergence and extension movements, trilobite regulates mediolateral cell polarity underlying effective intercalation and directed dorsal migration at increasing velocities. In the hindbrain, trilobite controls effective migration of branchiomotor neurons towards posterior rhombomeres. Mosaic analyses show trilobite functions cell-autonomously and non-autonomously in gastrulae and the hindbrain. We propose Trilobite/Stbm mediates cellular interactions that confer directionality on distinct movements during vertebrate embryogenesis.
胚胎形态发生由一系列细胞行为驱动,包括协调的形状变化、细胞重排和单个细胞迁移,其分子决定因素大多未知。在斑马鱼(Danio rerio)中,三叶虫突变胚胎在原肠胚形成运动和后脑神经元的向后迁移方面存在缺陷。在这里,我们利用定位克隆证明,三叶虫突变破坏了跨膜蛋白斜视(Stbm)/梵高(Vang),该蛋白先前与果蝇的平面细胞极性(PCP)以及脊椎动物的PCP和经典Wnt/β-连环蛋白信号传导有关。我们的遗传和分子分析表明,在原肠胚形成过程中,三叶虫与PCP途径相互作用而不影响经典Wnt信号传导。此外,三叶虫可能独立于PCP分子调节神经元迁移。我们表明,三叶虫介导不同运动行为的极化。在原肠胚形成的汇聚和延伸运动中,三叶虫调节有效插入和以增加的速度定向背侧迁移所依赖的中外侧细胞极性。在后脑中,三叶虫控制鳃运动神经元向后菱脑节的有效迁移。镶嵌分析表明,三叶虫在原肠胚和后脑中以细胞自主和非自主方式发挥作用。我们提出,三叶虫/Stbm介导细胞间相互作用,在脊椎动物胚胎发育过程中赋予不同运动方向性。