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Molecular and genetic analysis of the extracellular matrix during Drosophila development

Mechanisms of bicoid mRNA gradient formation.

Cancer in Drosophila: a novel genetic screen.

Molecular and genetic analysis of Drosophila dystroglycan, a regulator of epithelial polarity.

Embryology and molecular biology of the blow fly Lucilia sericata.

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The assessment used for to define neoplasia in Drosophila are quite similar to those used by clinical tumour pathologists: 1) in situ cell overproliferation, 2) altered cell morphology, 3) loss or decrease of differentiation capacity, 4) in situ invasiveness, and 5) transplantability.

In Drosophila, mutations in over 100 genes have been identified in which loss-of-function mutations lead to excess cell proliferation in the embryo, in the central nervous system, imaginal discs or hematopoietic organs of the larva, or in the adult gonads. 32 of these genes have been cloned and characterised at the molecular level, and 15 nine of them show clear homology to mammalian genes. Most of these mammalian genes had not been previously implicated in cell proliferation control. Overgrowth in some of these mutants involves conversion to a cell type that, in normal development, shows more cell proliferation than the original cell type. For example, the neurogenic mutants, including Notch, show conversion of epidermal cells to neuroblasts, leading to the neurogenic phenotype of excess nervous tissue. The ovarian tumour mutants show a conversion of the female germ line to a cell type resembling the male germ line which undergoes more proliferation than the female germ line.

A recently developed universal germline transformation system, developed by the neighboring Häcker lab, was adapted to allow insertional mutagenesis in Drosophila. Because the system relies on piggyBac and Hermes transposons, insertional mutagenesis can be targeted directly to FRT chromosomes without mobilizing the P-elements harbouring the FRTs.

The genetic approach aims at isolating recessive over-proliferation mutations which are obtained by screening clones of mutant cells in genetic mosaics in Drosophila. By using a simple model system, it is envisaged that basic knowledge will be accumulated that can be applied also for higher organisms, as many as 80 % of the molecules and the mechanisms they are involved in show a high degree of conservation between the fly and humans. Thus, Drosophila is an excellent model system for studying the molecular mechanisms of tumorigenesis and directly contributes to our understanding of cancer biology.

The screen yielded 15 cancer fly lines so far, each line showing different kind of tumors: