CELLULAR & MOLECULAR STUDIES OF THE DIFFUSE ENDOCRINE SYSTEM

项目摘要/摘要 果蝇中肠为了解哺乳动物的胃肠道提供了一个有用的模型。在将肠道微生物群落的特定结构与不同的生理状态联系起来方面已经取得了很大的进展。然而，嵌入肠道上皮的肠内分泌细胞是如何对这些动态变化的微生物线索做出反应的，人们还不太清楚。我们的初步研究为建立一个强大的新的果蝇肠道内分泌系统模型奠定了基础。这些观察结果提出了一个中心假设，即内分泌细胞通过远程信号来控制远处组织的动态平衡。我们建议描述肠内分泌细胞向周围组织发出信号的机制(S)。这些问题目前在哺乳动物中很难解决，因为有条件地操作内分泌细胞亚型和具有单细胞分辨率的外周靶组织的工具尚未建立。因此，我们建议以果蝇为模型来剖析控制内分泌系统的机制。

PROJECT SUMMARY/ABSTRACT The Drosophila midgut provides a useful model for understanding the mammalian gastrointestinal tract. Great progress has been made in associating specific configurations of our gut microbial communities with distinct physiological states. Yet, precisely how enteroendocrine cells embedded in the gut epithelium signal peripheral tissues in response to these dynamically changing microbial cues is less well understood. Our preliminary studies have laid the foundation for a powerful new Drosophila model of the enteroendocrine system. These observations raise the central hypothesis that endocrine cells signal over a long-range to control homeostasis of distant tissues. We propose to characterize the mechanism(s) by which enteroendocrine cells signal peripheral tissues. These questions are currently difficult to address in mammals, as the tools for conditionally manipulating both endocrine cell subtypes and peripheral target tissues with single cell resolution have not yet been established. Thus, we propose to use Drosophila as a model to dissect mechanisms controlling the endocrine system.