Hedgehog Signaling in Development and Metabolism

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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.