内臓筋細胞における核移動の左右極性化を起源とする左右非対称性形成の新規機構の研究

内脏肌细胞核迁移左右极化导致左右不对称形成的新机制研究

• 批准号: 19J10986
• 负责人: LAI YI TING
• 金额: $ 1.22万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2019
• 资助国家: 日本
• 起止时间: 2019-04-25 至 2021-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19J10986/
• 关键词: 左右非対称性; ショウジョウバエ; JAK/STATシグナル

The molecular mechanism of left-right (LR) asymmetric development is a principal question in developmental biology. Many of the internal organs of Drosophila melanogaster show stereotypical LR asymmetry, for which the underlying mechanisms are still elusive. In this study, I found that the LR-asymmetric morphogenesis of the embryonic foregut and midgut requires AWP1/doctor no (drn), a novel regulator of Drosophila JAK/STAT signaling. I showed that drn is essential in the circular visceral muscle cells of the midgut for regulating JAK/STAT signaling, which contributes to LR-asymmetric cells rearrangement during development. The product of drn is an A20/AN1-type zinc finger protein which was observed ubiquitously in the embryo. My results suggested that Drn interacts directly or indirectly with some proteins of the Rab GTPase family. Therefore, Drn may play a role in the regulation of intracellular trafficking of vesicles. The absence of Drn resulted in the accumulation of Domeless (Dome), the JAK/STAT signaling receptor of Drosophila, around the plasma membrane. These results indicate that Drn can promote the endocytic trafficking of Dome, which is a process required for the activation of JAK/STAT signaling activity in the embryo. Overall, this study presents a working model of drn, a novel gene required for the strict regulation of JAK/STAT signaling through the control of endocytic trafficking, which is involved in LR-asymmetric morphogenesis in the Drosophila anterior gut.

左右不对称发育的分子机制是发育生物学研究的重要课题。果蝇的许多内部器官表现出典型的LR不对称性，其潜在的机制仍然难以捉摸。在这项研究中，我发现胚胎前肠和中肠的LR不对称形态发生需要AWP 1/doctor no（drn），这是果蝇JAK/STAT信号的一种新调节剂。我表明，drn是必不可少的，在循环内脏肌细胞的中肠调节JAK/STAT信号，这有助于LR不对称细胞重排在发展过程中。drn的产物是A20/AN 1型锌指蛋白，其在胚胎中普遍存在。我的结果表明Drn与Rab GTPase家族的一些蛋白质直接或间接相互作用。因此，Drn可能在调节囊泡的胞内运输中发挥作用。Drn的缺失导致果蝇的JAK/STAT信号受体Domeless（Dome）在质膜周围积累。这些结果表明，Drn可以促进Dome的内吞运输，这是激活胚胎中JAK/STAT信号传导活性所需的过程。总的来说，这项研究提出了一个工作模型的drn，一种新的基因需要严格的JAK/STAT信号通过控制内吞运输，这是参与LR不对称形态发生在果蝇前肠。

项目成果

A noncoding mutation, narigoma, reveals a key regulator of gut left-right asymmetry in Drosophila melanogaster

非编码突变 narigoma 揭示了果蝇肠道左右不对称的关键调节因子

• 发表时间: 2019
• 作者: Daido Ryuji;Ho Shu-Yu;Takahashi Fuminobu;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Yi-Ting Lai
• 通讯作者: Yi-Ting Lai

Characterization of narigoma, a key regulator of anterior gut left-right asymmetry in Drosophila melanogaster

果蝇前肠左右不对称的关键调节因子 narigoma 的表征

• 发表时间: 2019
• 作者: Daido Ryuji;Ho Shu-Yu;Takahashi Fuminobu;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Shu-Yu Ho;Yi-Ting Lai;Yi-Ting Lai
• 通讯作者: Yi-Ting Lai