Lee Hanee, Kang Junsu, Lee Junho
Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul, Korea 08826.
Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul, Korea 08826
G3 (Bethesda). 2018 Jul 31;8(8):2595-2602. doi: 10.1534/g3.118.200325.
Guidance molecules, receptors, and downstream signaling pathways involved in the asymmetric neuronal cell migration and process outgrowth have been identified from genetic studies using model organisms, most of which are evolutionarily conserved. In the nematode , the roles of Wnt ligands and their receptors in the polarization of specific sets of neurons along the anterior-posterior (A-P) body axis have been well elucidated, but their downstream effectors are relatively unknown. Here, we report , encoding an evolutionarily conserved transcriptional co-activator, as a novel player in the Wnt-mediated asymmetric development of specific neurons in We found that the loss of activity failed to restrict the dendritic extension of ALM neurons to the anterior orientation, which is similar to the phenotype caused by defective and Wnt gene activities. Cell-specific rescue experiments showed that acts in the cell autonomous manner to polarize ALM dendrites. We also found that subcellular localization of YAP-1 was spatio-temporally regulated. The loss of in Wnt-deficient mutants did not increase the severity of the ALM polarity defect of the mutants. Wnt-deficient animals displayed abnormal subcellular localization of YAP-1 in touch receptor neurons, suggesting that may act downstream of the Wnt ligands for the ALM polarization process. Together, we have identified a new role for YAP-1 in neuronal development and our works will contribute to further understanding of intracellular events in neuronal polarization during animal development.
从使用模式生物的遗传研究中已鉴定出参与不对称神经元细胞迁移和轴突生长的导向分子、受体及下游信号通路,其中大多数在进化上是保守的。在线虫中,Wnt配体及其受体在特定神经元组沿前后(A-P)体轴极化中的作用已得到充分阐明,但其下游效应器相对未知。在此,我们报道了一种编码进化上保守的转录共激活因子的基因,它是Wnt介导的特定神经元不对称发育中的一个新角色。我们发现该基因活性的丧失未能将ALM神经元的树突延伸限制在前向,这与Wnt基因活性缺陷导致的表型相似。细胞特异性拯救实验表明,该基因以细胞自主方式使ALM树突极化。我们还发现YAP-1的亚细胞定位受到时空调节。在Wnt缺陷突变体中该基因的缺失并未增加突变体ALM极性缺陷的严重程度。Wnt缺陷动物在触觉受体神经元中显示出YAP-1异常的亚细胞定位,这表明该基因可能在Wnt配体下游参与ALM极化过程。总之,我们确定了YAP-1在神经元发育中的新作用,我们的工作将有助于进一步理解动物发育过程中神经元极化的细胞内事件。