Exosome-mediated cell-cell signaling in Rett Syndrome

描述(申请人提供)：Rett综合征中外切体介导的细胞-细胞通讯功能神经回路的发展需要一系列复杂的事件，涉及多种细胞类型之间在多个空间和时间维度上的协调通讯。细胞外膜囊泡(EMVS)，特别是外切体，可能在脑发育过程中作为一种新的细胞-细胞通讯形式。胞外体可以在细胞之间转移生物活性的脂类、蛋白质和RNA，而不需要供体和受体细胞之间的直接接触。到目前为止，还没有研究表明外切体在大脑发育中发挥作用，或者外切体信号的缺陷可能是导致Rett综合征等神经发育障碍的原因。我们建议使用小鼠和HiPSC模型来解决这些基本的开放问题，即外切体在Rett综合征和健康神经元的脑回路发育中的潜在作用。

DESCRIPTION (provided by applicant): Exosome-mediated cell-cell communication in Rett Syndrome Development of functional neuronal circuits requires a complex series of events involving coordinated communication between multiple cell types over multiple dimensions of space and time. Extracellular membrane vesicles (EMVs), specifically exosomes, may serve as a novel form of cell-cell communication during brain development. Exosomes can transfer bioactive lipids, proteins, and RNAs between cells without requiring direct contact between the donor and recipient cells. So far, no studies have demonstrated that exosomes play a role in brain development or that deficits in exosome signaling might underlie neurodevelopmental disorders such as Rett Syndrome. We propose to address these fundamental open questions regarding the potential role of exosomes in brain circuit development in Rett Syndrome and healthy neurons using both mouse and hiPSC models.