Canonical Wnt signaling exerts bidirectional control on choroid plexus epithelial development

The choroid plexus (CP) secretes cerebrospinal fluid and is critical for the development and function of the brain. In the telencephalon, the CP epithelium (CPe) arises from the Wnt- and Bmp- expressing cortical hem. We examined the role of canonical Wnt signaling in CPe development and report that the mouse and human embryonic CPe expresses molecules in this pathway. Either loss of function or constitutive activation of β-catenin, a key mediator of canonical Wnt signaling, causes a profound disruption of mouse CPe development. Loss of β-catenin results in a dysmorphic CPe, while constitutive activation of β-catenin causes a loss of CPe identity and a transformation of this tissue to a hippocampal-like identity. Aspects of this phenomenon are recapitulated in human embryonic stem cell (hESC)-derived organoids. Our results indicate that canonical Wnt signaling is required in a precisely regulated manner for normal CP development in the mammalian brain. Wnt Gain of function Chorid plexus and hippocampus were dissected and processed for RNA seq

脉络丛（choroid plexus, CP）可分泌脑脊液，对大脑的发育与功能至关重要。在端脑内，脉络丛上皮（choroid plexus epithelium, CPe）起源于表达Wnt与Bmp的皮质边缘区（cortical hem）。我们探究了经典Wnt信号通路在CPe发育中的作用，研究发现小鼠与人类胚胎的CPe均可表达该通路中的相关分子。作为经典Wnt信号通路的关键介导因子，β-连环蛋白（β-catenin）的功能缺失或组成型激活，均会严重扰乱小鼠CPe的发育过程。β-连环蛋白功能缺失会导致CPe形态异常，而其组成型激活则会使CPe丧失自身细胞身份，并将该组织转化为类似海马的细胞身份。该现象的部分特征可在人类胚胎干细胞（human embryonic stem cell, hESC）衍生的类器官中重现。本研究结果表明，哺乳动物大脑的正常CP发育需要经典Wnt信号通路受到精确调控。我们对Wnt功能获得性样本的脉络丛与海马组织进行了解剖分离，并开展RNA测序（RNA-seq）分析。