神经胶质蛋白通过增强表皮生长因子受体信号来调节果蝇肠道干细胞的增殖。
Neuroglian regulates Drosophila intestinal stem cell proliferation through enhanced signaling via the epidermal growth factor receptor.
机构信息
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
出版信息
Stem Cell Reports. 2021 Jun 8;16(6):1584-1597. doi: 10.1016/j.stemcr.2021.04.006. Epub 2021 May 6.
The Drosophila intestine is an excellent system for elucidating mechanisms regulating stem cell behavior. Here we show that the septate junction (SJ) protein Neuroglian (Nrg) is expressed in intestinal stem cells (ISCs) and enteroblasts (EBs) within the fly intestine. SJs are not present between ISCs and EBs, suggesting Nrg plays a different role in this tissue. We reveal that Nrg is required for ISC proliferation in young flies, and depletion of Nrg from ISCs and EBs suppresses increased ISC proliferation in aged flies. Conversely, overexpression of Nrg in ISC and EBs promotes ISC proliferation, leading to an increase in cells expressing ISC/EB markers; in addition, we observe an increase in epidermal growth factor receptor (Egfr) activation. Genetic epistasis experiments reveal that Nrg acts upstream of Egfr to regulate ISC proliferation. As Nrg function is highly conserved in mammalian systems, our work characterizing the role of Nrg in the intestine has implications for the treatment of intestinal disorders that arise due to altered ISC behavior.
果蝇肠道是阐明调控干细胞行为机制的极佳系统。在这里，我们发现，位于果蝇肠道内的干细胞（ISCs）和肠母细胞（EBs）中表达了 神经钙黏蛋白（Neuroglian，Nrg）这一隔膜连接蛋白。ISCs 和 EBs 之间并不存在隔膜连接，这表明 Nrg 在这种组织中发挥了不同的作用。我们揭示，Nrg 在年轻果蝇的 ISC 增殖中是必需的，而从 ISCs 和 EBs 中去除 Nrg 会抑制年老果蝇中 ISC 增殖的增加。相反，Nrg 在 ISC 和 EBs 中的过表达促进了 ISC 的增殖，导致表达 ISC/EB 标志物的细胞增加；此外，我们观察到表皮生长因子受体（Egfr）的激活增加。遗传上位性实验表明，Nrg 通过作用于 Egfr 上游来调节 ISC 的增殖。由于 Nrg 在哺乳动物系统中的功能高度保守，我们对 Nrg 在肠道中的作用进行了特征描述，这对于治疗由于 ISC 行为改变而引起的肠道疾病具有重要意义。
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