This project deals with molecular and genetic studies of the genes functioning in hedgehog signaling, shanti and oroshigane. hedgehog signaling is an important signal transduction pathway in most eukaryotes. The hedgehog protein, a secreted molecule, regulates a state of gene expression in the cells that receive it. The hedgehog signal pathway consists of many molecules from a receptor in the plasma membrane to a transcription factor in the nucleus.
Cuticle pattern (ventral view) of a wild type larva. Notice the regularly spaced rows of small bristles called setae. They are named denticle belts and are seen in eight abdominal segments. This is a dead embryo of an oroshigane mutant. Patterns of denticle belts are different from those of wild type. They show a somewhat mirror-imaged pattern, which resembles those of hedgehog mutant embryos (see right). This is a hedghog mutant embryo. They lose naked cuticle surface and filled with setae. This is a typical pattern of mutations that belong to segment-polarilty genes. oroshigane and hedgehog belong to this class.
In order to understand how hedgehog signaling works, we must know all the molecules involved in this pathway. There may be several sets of different molecules for signaling depending on tissues and different developmental stages. Like hedgehog, oroshigane and shanti mutations are lethal, which indicates that they are essential genes for Drosophila. Moreover, dead mutant embryos exhibit defective body patterns similar to those of hedgehog mutations. In genetics, this result can be interpreted that they function in the hedgehog signal pathway. My goal in this project is to pinpoint at which step in the hedgehog pathway these molecules work. I have cloned these genes and am now exploring how these molecules work at the molecular level. For this purpose, we examine the cells with and without shanti and oroshigane functions using genetic, biochemical, molecular and histological tools.
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