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

左右不对称发育的分子机制是发育生物学中的一个重要问题。黑腹果蝇的许多内部器官表现出典型的LR不对称，其潜在机制尚不清楚。在本研究中，我发现胚胎前肠和中肠的lr -不对称形态发生需要AWP1/doctor no (drn)，这是果蝇JAK/STAT信号的一种新型调节因子。我发现drn在中肠的环状内脏肌细胞中对调节JAK/STAT信号至关重要，这有助于发育过程中lr -不对称细胞重排。drn的产物是一种A20/ an1型锌指蛋白，在胚胎中普遍存在。我的研究结果表明Drn直接或间接地与Rab GTPase家族的一些蛋白相互作用。因此，Drn可能在调节囊泡的细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信号活性所必需的过程。总的来说，本研究提出了一个drn的工作模型，drn是一个通过控制内吞运输来严格调控JAK/STAT信号的新基因，参与果蝇前肠lr -不对称形态发生。

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.