Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
PLoS Biol. 2011 Sep;9(9):e1001157. doi: 10.1371/journal.pbio.1001157. Epub 2011 Sep 20.
Nervous system function requires proper development of two functional and morphological domains of neurons, axons and dendrites. Although both these domains are equally important for signal transmission, our understanding of dendrite development remains relatively poor. Here, we show that in C. elegans the Wnt ligand, LIN-44, and its Frizzled receptor, LIN-17, regulate dendrite development of the PQR oxygen sensory neuron. In lin-44 and lin-17 mutants, PQR dendrites fail to form, display stunted growth, or are misrouted. Manipulation of temporal and spatial expression of LIN-44, combined with cell-ablation experiments, indicates that this molecule is patterned during embryogenesis and acts as an attractive cue to define the site from which the dendrite emerges. Genetic interaction between lin-44 and lin-17 suggests that the LIN-44 signal is transmitted through the LIN-17 receptor, which acts cell autonomously in PQR. Furthermore, we provide evidence that LIN-17 interacts with another Wnt molecule, EGL-20, and functions in parallel to MIG-1/Frizzled in this process. Taken together, our results reveal a crucial role for Wnt and Frizzled molecules in regulating dendrite development in vivo.
神经系统的功能需要神经元的两个功能和形态域，轴突和树突的适当发育。虽然这两个域对于信号传递都同样重要，但我们对树突发育的理解仍然相对较差。在这里，我们表明在秀丽隐杆线虫中，Wnt 配体 LIN-44 和其 Frizzled 受体 LIN-17 调节 PQR 氧感觉神经元的树突发育。在 lin-44 和 lin-17 突变体中，PQR 树突不能形成，显示出生长迟缓，或被错误引导。LIN-44 的时空表达的操纵，结合细胞消融实验，表明这种分子在胚胎发生期间被模式化，并作为吸引线索来定义树突出现的位置。lin-44 和 lin-17 之间的遗传相互作用表明，LIN-44 信号通过 LIN-17 受体传递，该受体在 PQR 中自主发挥作用。此外，我们提供了证据表明 LIN-17 与另一个 Wnt 分子 EGL-20 相互作用，并在这个过程中与 MIG-1/Frizzled 平行发挥作用。总之，我们的结果揭示了 Wnt 和 Frizzled 分子在体内调节树突发育中的关键作用。
