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Control of tissue growth: elucidation of the Hippo signaling pathway
A selection of talks on Genetics & Epigenetics
Genetic counseling: preconception, prenatal, perinatal
- Prof. Aubrey Milunsky
- Tufts University School of Medicine, USA
Recent advances in the development of gene delivery technologies
- Dr. Takis Athanasopoulos
- GSK, UK
My name is DJ Pan, I am a faculty member in the Department of Molecular Biology and Genetics at Johns Hopkins University School of Medicine. In today's lecture I will review recent studies in the fruit fly Drosophila concerning the control of tissue growth. In particular my lecture will focus on the recent elucidation of a novel signalling pathway which we call the 'Hippo pathway'. It's my hope that this lecture will provide you with an example of how one can use the fruit fly as a powerful model to understand the basic mechanisms of human disease, including the mechanisms of human cancer.
During organogenesis, growth and patterning must be independently coordinated in order to generate organs of reproducible size and shape. Compared to our understanding of pattern formation, relatively less is known about how the size of an organ is determined. The compound eye of Drosophila is an ideal system to study organ size, since this organ is totally dispensable for animal viability. This means one can screen for mutations that increase or decrease the size of an eye without worrying about the detrimental effects of the mutation on animal viability.
In the last decade, many Drosophila labs have conducted genetic screens for growth regulators of the compound eye using mosaic flies. The essence of these screens is to generate, by mitotic recombination, a cell that is homozygous for a given mutation in an otherwise heterozygous mutant background. These screens are set up in such a way that whenever a homozygous mutant cell (designated here as minus over minus or -/-) is generated, a sibling cell is also generated which has a plus over plus (+/+) genotype. This pair of cells then proliferates to generate two clones of cells next to each other in the adult eye. If a gene does not play a role in tissue growth, we might expect the mutant clone to be of the same size as a sibling clone. However if a gene normally is positively required for tissue growth we might expect the mutant clone to be smaller than the sibling clone. On the contrary, if a gene normally plays a negative role in growth control then we might expect a mutant clone to be larger than the sibling clone. This last class of overgrown mutation represents what we call the tumor suppressor genes.