The choroid plexus (CP) is the predominant supplier of cerebral spinal fluid (CSF) and the site of the blood-CSF barrier and is thus essential for brain development and central nervous system homeostasis. Despite these crucial roles, our understanding of the molecular and cellular processes giving rise to the CPs within the ventricles of the mammalian brain is very rudimentary. Here, we identify WNT5a as an important regulator of CP development, where it acts as a pivotal factor driving CP epithelial morphogenesis in all ventricles. We show that WNT5a is essential for the establishment of a cohesive epithelium in the developing CP. We find that in its absence all CPs are substantially reduced in size and complexity and fail to expand into the ventricles. Severe defects were observed in the epithelial cytoarchitecture of all Wnt5a-/- CPs, exemplified by loss of apicobasally polarized morphology and detachment from the ventricular surface and/or basement membrane. We also present evidence that the WNT5a receptor, RYK, and the RHOA kinase, ROCK, are required for normal CP epithelial morphogenesis. Our study, therefore, reveals important insights into the molecular and cellular mechanisms governing CP development.

中文翻译：

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WNT5a 调节发育中的脉络丛中的上皮形态发生。

脉络丛 (CP) 是脑脊液 (CSF) 的主要供应者，也是血-CSF 屏障的部位，因此对于大脑发育和中枢神经系统稳态至关重要。尽管有这些关键作用，但我们对哺乳动物大脑脑室内产生 CP 的分子和细胞过程的理解非常初级。在这里，我们将 WNT5a 确定为 CP 发育的重要调节因子，它是驱动所有心室 CP 上皮形态发生的关键因素。我们表明 WNT5a 对于在发育中的 CP 中建立粘性上皮至关重要。我们发现，在没有它的情况下，所有 CP 的大小和复杂性都大大减少，并且无法扩展到心室。在所有 Wnt5a-/- CP 的上皮细胞结构中观察到严重缺陷，例如顶端极化形态的丧失和心室表面和/或基底膜的脱离。我们还提供了 WNT5a 受体 RYK 和 RHOA 激酶 ROCK 是正常 CP 上皮形态发生所必需的证据。因此，我们的研究揭示了对控制 CP 发育的分子和细胞机制的重要见解。