Research Institute for Molecular Pathology (IMP), Vienna Biocenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria; DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany.
DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany.
Stem Cell Reports. 2018 Jun 5;10(6):1751-1765. doi: 10.1016/j.stemcr.2018.04.018. Epub 2018 May 17.
In the developing nervous system, neural stem cells are polarized and maintain an apical domain facing a central lumen. The presence of apical membrane is thought to have a profound influence on maintaining the stem cell state. With the onset of neurogenesis, cells lose their polarization, and the concomitant loss of the apical domain coincides with a loss of the stem cell identity. Little is known about the molecular signals controlling apical membrane size. Here, we use two neuroepithelial cell systems, one derived from regenerating axolotl spinal cord and the other from human embryonic stem cells, to identify a molecular signaling pathway initiated by lysophosphatidic acid that controls apical membrane size and consequently controls and maintains epithelial organization and lumen size in neuroepithelial rosettes. This apical domain size increase occurs independently of effects on proliferation and involves a serum response factor-dependent transcriptional induction of junctional and apical membrane components.
在发育中的神经系统中，神经干细胞具有极性，并维持一个朝向中央腔的顶端区域。顶端膜的存在被认为对维持干细胞状态有深远的影响。随着神经发生的开始，细胞失去极化，顶端区域的同时丧失与干细胞特性的丧失相一致。关于控制顶端膜大小的分子信号知之甚少。在这里，我们使用两种神经上皮细胞系统，一种来自再生的蝾螈脊髓，另一种来自人类胚胎干细胞，来鉴定由溶血磷脂酸引发的分子信号通路，该通路控制顶端膜的大小，并因此控制和维持神经上皮玫瑰花结中的上皮组织和腔大小。这种顶端区域大小的增加独立于对增殖的影响，并且涉及到一个血清反应因子依赖性的连接和顶端膜成分的转录诱导。
