Neuroglian regulates Drosophila intestinal stem cell proliferation through enhanced signaling via the epidermal growth factor receptor.
Neuroglian regulates Drosophila intestinal stem cell proliferation through enhanced signaling via the epidermal growth factor receptor.
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DOI：
10.1016/j.stemcr.2021.04.006
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发表时间：
2021-06-08
影响因子：
5.9
通讯作者：
Jones DL
中科院分区：
文献类型：
--
作者：
Resnik-Docampo M;Cunningham KM;Ruvalcaba SM;Choi C;Sauer V;Jones DL
果蝇肠道是阐明调节干细胞行为机制的一个很好的系统。本研究表明，分离连接（SJ）蛋白Neuroglian （Nrg）在果蝇肠道内的肠干细胞（ISCs）和肠母细胞（EBs）中表达。在ISCs和EBs之间不存在SJs，这表明Nrg在该组织中起着不同的作用。我们发现Nrg是幼龄果蝇ISC增殖所必需的，并且来自ISC和EBs的Nrg的消耗抑制了老年果蝇ISC增殖的增加。相反，在ISC和EBs中过表达Nrg可促进ISC增殖，导致表达ISC/EB标志物的细胞数量增加；此外，我们观察到表皮生长因子受体（Egfr）激活增加。遗传上位实验表明，Nrg作用于Egfr上游调控ISC增殖。由于Nrg的功能在哺乳动物系统中是高度保守的，我们对Nrg在肠道中的作用的研究对治疗由ISC行为改变引起的肠道疾病具有重要意义。Nrg在果蝇中肠的ISCs和EBs中表达，Nrg是ISC增殖的必要和充分条件，随着年龄的增长，Nrg的表达增加，驱动ISC增殖和肠道发育不良，Nrg通过增强EGFR信号传导来调节ISC增殖。在这篇文章中，Jones和他的同事证明，神经胶质细胞（Neuroglian, Nrg）在果蝇中肠的肠干细胞（ISCs）和肠母细胞中表达，通过EGFR调节ISC增殖。此外，数据表明，随着年龄的增长，Nrg表达的增加有助于ISC增殖和肠道发育不良。这些发现表明Nrg-EGFR信号在肠道中的作用，可能与年龄相关疾病有关。
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. Nrg is expressed in ISCs and EBs of the Drosophila midgut Nrg is necessary and sufficient for ISC proliferation Increased Nrg expression with age drives ISC proliferation and intestinal dysplasia Nrg acts to potentiate EGFR signaling in order to regulate ISC proliferation In this article, Jones and colleagues demonstrate that Neuroglian (Nrg) is expressed in intestinal stem cells (ISCs) and enteroblasts of the Drosophila midgut, where it regulates ISC proliferation via the EGFR. Furthermore, data suggest that increased Nrg expression during aging contributes to ISC proliferation and intestinal dysplasia. These findings suggest a role for Nrg-EGFR signaling in the intestine, which could be implicated in age-related disease.
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影响因子：
3.7
作者：
Kudumala S;Freund J;Hortsch M;Godenschwege TA
通讯作者：
Godenschwege TA
影响因子：
9.8
作者：
Enneking EM;Kudumala SR;Moreno E;Stephan R;Boerner J;Godenschwege TA;Pielage J
通讯作者：
Pielage J
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
4
作者：
Gavert, Nancy;Ben-Shmuel, Amir;Ben-Ze'ev, Avri
通讯作者：
Ben-Ze'ev, Avri
L1 是 β-连环蛋白信号传导的新靶标，可转化细胞并在结肠癌的侵袭性前沿表达。
影响因子：
7.8
作者：
Gavert, N;Conacci-Sorrell, M;Gast, D;Schneider, A;Altevogt, P;Brabletz, T;Ben-Ze'ev, A
通讯作者：
Ben-Ze'ev, A