CELLULAR & MOLECULAR STUDIES OF THE DIFFUSE ENDOCRINE SYSTEM

项目总结/摘要 果蝇中肠为了解哺乳动物胃肠道提供了一个有用的模型。在将我们肠道微生物群落的特定配置与不同的生理状态相关联方面取得了很大进展。然而，确切地说，嵌入肠道上皮的肠内分泌细胞是如何响应这些动态变化的微生物线索而向外周组织发出信号的，还不太清楚。我们的初步研究奠定了基础，一个强大的新的果蝇模型的肠内分泌系统。这些观察结果提出了一个中心假设，即内分泌细胞发出长距离信号，以控制远处组织的稳态。我们提出了肠内分泌细胞信号的外周组织的机制的特点。这些问题目前在哺乳动物中难以解决，因为用于以单细胞分辨率有条件地操纵内分泌细胞亚型和外周靶组织的工具尚未建立。因此，我们建议使用果蝇作为一个模型来解剖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.