Organisti Cristina, Hein Irina, Grunwald Kadow Ilona C, Suzuki Takashi
Max Planck Institute of Neurobiology, Sensory Neurogenetics Research Group, Am Klopferspitz 18, Martinsried, 82152, Germany.
Genes Cells. 2015 Jan;20(1):50-67. doi: 10.1111/gtc.12202. Epub 2014 Nov 30.
During central nervous system development, several guidance cues and receptors, as well as cell adhesion molecules, are required for guiding axons across the midline and along the anterior-posterior axis. In Drosophila, commissural axons sense the midline attractants Netrin A and B (Net) through Frazzled (Fra) receptors. Despite their importance, lack of Net or fra affects only some commissures, suggesting that additional molecules can fulfill this function. Recently, planar cell polarity (PCP) proteins have been implicated in midline axon guidance in both vertebrate and invertebrate systems. Here, we report that the atypical cadherin and PCP molecule Flamingo/Starry night (Fmi/Stan) acts jointly with Net/Fra signaling during midline development. Additional removal of fmi strongly increases the guidance defects in Net/fra mutants. Rescue and domain deletion experiments suggest that Fmi signaling facilitates commissural pathfinding potentially by mediating axonal fasciculation in a partly homophilic manner. Altogether, our results indicate that contact-mediated cell adhesion via Fmi acts in addition to the Net/Fra guidance system during axon pathfinding across the midline, underlining the importance of PCP molecules during vertebrates and invertebrates midline development.
在中枢神经系统发育过程中，轴突穿越中线并沿前后轴生长需要多种导向线索、受体以及细胞黏附分子。在果蝇中，连合轴突通过Frazzled（Fra）受体感知中线吸引因子Netrin A和B（Net）。尽管它们很重要，但缺乏Net或fra仅影响部分连合，这表明其他分子也能履行这一功能。最近，平面细胞极性（PCP）蛋白已被证明在脊椎动物和无脊椎动物系统的中线轴突导向中发挥作用。在此，我们报道非典型钙黏蛋白和PCP分子Flamingo/Starry night（Fmi/Stan）在中线发育过程中与Net/Fra信号共同发挥作用。额外去除fmi会显著增加Net/fra突变体中的导向缺陷。拯救和结构域缺失实验表明，Fmi信号可能通过部分同源性方式介导轴突成束，从而促进连合轴突的路径寻找。总之，我们的结果表明，在轴突穿越中线的路径寻找过程中，除了Net/Fra导向系统外，通过Fmi进行的接触介导的细胞黏附也发挥作用，这突出了PCP分子在脊椎动物和无脊椎动物中线发育中的重要性。
