Fung Wendy, Tan Taralyn M, Kolotuev Irina, Heiman Maxwell G
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.
bioRxiv. 2023 Mar 18:2023.03.17.533199. doi: 10.1101/2023.03.17.533199.
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.
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。