通过无心脏 FGF 受体信号通路的神经元-胶质细胞相互作用,介导果蝇星形胶质细胞的形态发生。

Neuron-glia interactions through the Heartless FGF receptor signaling pathway mediate morphogenesis of Drosophila astrocytes.

机构信息

Department of Neurobiology, University of Massachusetts Medical School, Howard Hughes Medical Institute, Worcester, MA 01605, USA.

Department of Neurobiology, University of Massachusetts Medical School, Howard Hughes Medical Institute, Worcester, MA 01605, USA.

出版信息

Neuron. 2014 Jul 16;83(2):388-403. doi: 10.1016/j.neuron.2014.06.026.

Abstract

Astrocytes are critically important for neuronal circuit assembly and function. Mammalian protoplasmic astrocytes develop a dense ramified meshwork of cellular processes to form intimate contacts with neuronal cell bodies, neurites, and synapses. This close neuron-glia morphological relationship is essential for astrocyte function, but it remains unclear how astrocytes establish their intricate morphology, organize spatial domains, and associate with neurons and synapses in vivo. Here we characterize a Drosophila glial subtype that shows striking morphological and functional similarities to mammalian astrocytes. We demonstrate that the Fibroblast growth factor (FGF) receptor Heartless autonomously controls astrocyte membrane growth, and the FGFs Pyramus and Thisbe direct astrocyte processes to ramify specifically in CNS synaptic regions. We further show that the shape and size of individual astrocytes are dynamically sculpted through inhibitory or competitive astrocyte-astrocyte interactions and Heartless FGF signaling. Our data identify FGF signaling through Heartless as a key regulator of astrocyte morphological elaboration in vivo.

摘要

星形胶质细胞对于神经元回路的组装和功能至关重要。哺乳动物原浆性星形胶质细胞形成密集的分支细胞过程网络,与神经元胞体、神经突和突触形成紧密接触。这种密切的神经元-胶质形态关系对于星形胶质细胞的功能至关重要,但目前尚不清楚星形胶质细胞如何在体内建立其复杂的形态、组织空间域,并与神经元和突触相关联。在这里,我们描述了一种果蝇神经胶质亚型,它表现出与哺乳动物星形胶质细胞惊人的形态和功能相似性。我们证明,成纤维细胞生长因子 (FGF) 受体 Heartless 自主控制星形胶质细胞膜的生长,而 FGFs Pyramus 和 Thisbe 则直接引导星形胶质细胞的突起在中枢神经系统突触区域特异性分支。我们进一步表明,单个星形胶质细胞的形状和大小通过抑制性或竞争性星形胶质细胞-星形胶质细胞相互作用和 Heartless FGF 信号进行动态塑造。我们的数据表明,通过 Heartless 的 FGF 信号是体内星形胶质细胞形态发育的关键调节因子。

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