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单个神经胶质细胞中的性别特异性开关决定了顶端细胞外基质的模式。

A sex-specific switch in a single glial cell patterns the apical extracellular matrix.

作者信息

Fung Wendy, Tan Taralyn M, Kolotuev Irina, Heiman Maxwell G

机构信息

Department of Genetics, Blavatnik Institute, Harvard Medical School and Boston Children's Hospital, Boston, MA 02115, USA.

Electron Microscopy Facility, University of Lausanne, 1015 Lausanne, Switzerland.

出版信息

bioRxiv. 2023 Mar 18:2023.03.17.533199. doi: 10.1101/2023.03.17.533199.

Abstract

Apical extracellular matrix (aECM) constitutes the interface between every tissue and the outside world. It is patterned into diverse tissue-specific structures through unknown mechanisms. Here, we show that a male-specific genetic switch in a single glial cell patterns the aECM into a ∼200 nm pore, allowing a male sensory neuron to access the environment. We find that this glial sex difference is controlled by factors shared with neurons ( ) as well as previously unidentified regulators whose effects may be glia-specific ( ). The switch results in male-specific expression of a Hedgehog-related protein, GRL-18, that we discover localizes to transient nanoscale rings at sites of aECM pore formation. Blocking male-specific gene expression in glia prevents pore formation, whereas forcing male-specific expression induces an ectopic pore. Thus, a switch in gene expression in a single cell is necessary and sufficient to pattern aECM into a specific structure.

摘要

顶端细胞外基质(aECM)构成了每个组织与外界之间的界面。它通过未知机制形成各种组织特异性结构。在此,我们表明单个神经胶质细胞中的雄性特异性基因开关将aECM形成一个约200纳米的孔,使雄性感觉神经元能够接触外界环境。我们发现这种神经胶质细胞的性别差异受与神经元共享的因子( )以及以前未确定的调节因子控制,这些调节因子的作用可能是神经胶质细胞特异性的( )。该开关导致一种与刺猬蛋白相关的蛋白质GRL-18的雄性特异性表达,我们发现它定位于aECM孔形成部位的瞬时纳米级环上。阻断神经胶质细胞中雄性特异性基因的表达可防止孔的形成,而强制雄性特异性表达则会诱导异位孔的形成。因此,单个细胞中基因表达的转变对于将aECM形成特定结构是必要且充分的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d98/10055199/cb6be99e3523/nihpp-2023.03.17.533199v1-f0001.jpg

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