Aix Marseille University, CNRS, IBDM, Turing Center for Living Systems, Marseille 13009, France.
Aix Marseille University, CNRS, IBDM, Turing Center for Living Systems, Marseille 13009, France
Development. 2020 Apr 6;147(7):dev183186. doi: 10.1242/dev.183186.
Wnt/β-catenin signalling has been implicated in the terminal asymmetric divisions of neuronal progenitors in vertebrates and invertebrates. However, the role of Wnt ligands in this process remains poorly characterized. Here, we used the terminal divisions of the embryonic neuronal progenitors in to characterize the role of Wnt ligands during this process, focusing on a lineage that produces the cholinergic interneuron AIY. We observed that, during interphase, the neuronal progenitor is elongated along the anteroposterior axis, then divides along its major axis, generating an anterior and a posterior daughter with different fates. Using time-controlled perturbations, we show that three Wnt ligands, which are transcribed at higher levels at the posterior of the embryo, regulate the orientation of the neuronal progenitor and its asymmetric division. We also identify a role for a Wnt receptor (MOM-5) and a cortical transducer APC (APR-1), which are, respectively, enriched at the posterior and anterior poles of the neuronal progenitor. Our study establishes a role for Wnt ligands in the regulation of the shape and terminal asymmetric divisions of neuronal progenitors, and identifies downstream components.
Wnt/β-catenin 信号通路已被牵涉到脊椎动物和无脊椎动物中神经元祖细胞的终末不对称分裂中。然而,Wnt 配体在这个过程中的作用仍然知之甚少。在这里,我们利用 胚胎神经元祖细胞的终末分裂来研究 Wnt 配体在这个过程中的作用,重点关注产生胆碱能中间神经元 AIY 的谱系。我们观察到,在间期,神经元祖细胞沿前后轴拉长,然后沿着其长轴分裂,产生具有不同命运的前体细胞和后体细胞。通过时间控制的扰动实验,我们表明,三种在后胚胎中转录水平较高的 Wnt 配体调节神经元祖细胞的定向及其不对称分裂。我们还发现了一个 Wnt 受体(MOM-5)和一个皮质转导 APC(APR-1)的作用,它们分别在前体细胞的后极和前极富集。我们的研究确立了 Wnt 配体在调节神经元祖细胞的形状和终末不对称分裂中的作用,并确定了下游成分。