Hedgehog Signaling in Development and Metabolism

摘要： 现有的MIRA R35支持我们实验室的研究。我们专注于刺猬（Hh）信号 在模式形成和细胞生长控制中起关键作用的途径，也参与代谢 控制虽然Hh途径中的许多成分已经被鉴定出来，但Hh信号是如何转导的 通过12跨膜蛋白Patched（Ptc）到7跨膜蛋白Smoothened 对目前仍不清楚.我们研究计划的首要目标是了解Hh信号是如何被感知的， 传递以控制下游生物事件，最终控制细胞生长和图案化。果蝇 脂肪体和卵母细胞已成为研究脂质代谢和循环的有吸引力的模型。发表 在这些模型中的初步发现表明，脂质积累是由高度保守的 Hh信号通路不仅控制脂肪生成，而且通过调节特定的 基因.这些研究为研究Smo信号转导机制提供了新的工具和假设， Hh/Smo信号在调节脂质代谢中作用，与基底细胞癌等肿瘤的发生有关 癌和髓母细胞瘤。这种行政补充申请，以获得更高的质量 作为现有显微镜平台的附加组件，共聚焦系统将促进正在进行的实验， 研究计划。先进的扫描能力，除了更高的分辨率，新的共焦 该系统将显著提高成像分析的质量，以检查脂质代谢中的Hh信号传导。 调节脂肪体，并显着提高我们的能力，检查如何定位脂质和/或 胆固醇调节Smo在代谢组织如脂肪体中的丰度。

Abstract: The existing MIRA R35 is supporting the research in our laboratory. We focus on the Hedgehog (Hh) signaling pathway that plays critical roles in pattern formation and cell growth control and is also involved in metabolic control. While many components in the Hh pathway have been identified, how the Hh signal is transduced through the 12-span transmembrane protein Patched (Ptc) to the 7-span transmembrane protein Smoothened is still unclear. The overarching goal of our research program is to understand how Hh signals are sensed and transmitted to control downstream biological events that ultimately govern cell growth and patterning. Drosophila fat body and oenocyte have emerged as attractive models to study lipid metabolism and circulation. Published and preliminary findings in these models have indicated that lipid accumulation is regulated by highly conserved signaling pathways, and that Hh signaling controls not only lipogenesis but also lipolysis by regulating specific genes. These studies provide new tools and hypotheses for investigating the mechanisms of Smo signaling and the role of Hh/Smo signaling in regulating lipid metabolism, which relevance to such cancers as basal cell carcinoma and medulloblastoma. This administrative supplemental application to acquire a higher quality confocal system as an add-on to the existing microscope platform will foster the ongoing experiments in this research program. The advanced scanning capacities in addition to the higher resolution, the new confocal system will significantly improve the quality of the imaging analysis to examine Hh signaling in lipid metabolic regulation in the fat body and dramatically enhance our ability to examine how localization of lipids and/or cholesterol regulates Smo abundance in metabolic tissues, such as the fat body.