Analysis of cis-acting RNA sequences required for intracellular localisation of gurken,the Drosophila TGF alpha homologu

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Humans, flies and other multicellular animals, consist of many specialised cell types, located at their correct positions in the body. How such complex structures originate from the first simple cell, which is the fertilised oocyte or egg, has been a central question in biology. In the fruitfly, Drosophila, the first asymmetries arise when messenger RNA (mRNA) molecules that encode the information to make proteins, localise in specific places within the oocyte, and therefore target proteins to the same parts of the cell. How such mRNAs become restricted in their distribution is poorly understood. We will study how one key mRNA, gurken (grk) becomes localised to the dorsal (back) half of the egg and embryo, making it different from the ventral (front) half. Flies missing the grk gene lay eggs missing dorsal structures.We will use exciting new methods we have developed to make grk mRNA molecules emit red light in order to follow their localisation after injection into living fly oocytes and embryos (0.5mm long). We will image the cells of the oocyte and embryos using proteins that emit green light and define the signals in the mRNA that target it to its dorsal destination. We will also investigate what other genes are responsible for the localisation and how they achieve their function. Grk is related to the human transforming growth factor alpha (TGFa), which plays an important role in human oocyte maturation. TGFa is mutated in a number of different human cancers and developmental diseases. Before we can hope to cure such diseases, we must first understand how these molecules work, but studying the function of TGFa in humans is hampered by ethical and technical difficulties. Much more is known about these processes in Drosophila, in which many of the basic processes of development have turned out to be surprisingly similar to humans. We therefore anticipate that our work will be applicable to humans and may lead in the long term to a better understanding of how to cure diseases associated with malfunction of TGFa.