Schaller Research Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg 69120, Germany.
Electron Microscopy Facility, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole normale supérieure, CNRS, INSERM, PSL Research University, Paris 75005, France.
Dev Cell. 2023 Dec 4;58(23):2641-2651.e6. doi: 10.1016/j.devcel.2023.10.003. Epub 2023 Oct 26.
Choroid plexuses (ChPs) produce cerebrospinal fluid and sense non-cell-autonomous stimuli to control the homeostasis of the central nervous system. They are mainly composed of epithelial multiciliated cells, whose development and function are still controversial. We have thus characterized the stepwise order of mammalian ChP epithelia cilia formation using a combination of super-resolution-microscopy approaches and mouse genetics. We show that ChP ciliated cells are built embryonically on a treadmill of spatiotemporally regulated events, starting with atypical centriole amplification and ending with the construction of nodal-like 9+0 cilia, characterized by both primary and motile features. ChP cilia undergo axoneme resorption at early postnatal stages through a microtubule destabilization process controlled by the microtubule-severing enzyme spastin and mitigated by polyglutamylation levels. Notably, this phenotype is preserved in humans, suggesting a conserved ciliary resorption mechanism in mammals.
脉络丛(ChP)产生脑脊液并感知非细胞自主刺激,以控制中枢神经系统的内稳态。它们主要由上皮细胞纤毛细胞组成,其发育和功能仍存在争议。因此,我们使用超分辨率显微镜方法和小鼠遗传学的组合来描述哺乳动物 ChP 上皮纤毛形成的逐步顺序。我们表明,ChP 纤毛细胞在胚胎期是在时空调节事件的跑步机上构建的,首先是典型中心粒的扩增,最后是具有原发性和运动性特征的类似节点的 9+0 纤毛的构建。ChP 纤毛在出生后的早期阶段通过微管解聚酶 spastin 控制的微管不稳定过程进行轴突再吸收,并通过多聚谷氨酰胺化水平得到缓解。值得注意的是,这种表型在人类中得以保留,表明哺乳动物中存在保守的纤毛再吸收机制。