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

点击翻译按钮获取中文摘要

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.