The vertebrate limb constitutes a classic model for the study of developmental processes. Since it comprises a non-vital part of the embryo body, the limb bud can be readily manipulated without affecting survival. In addition, many molecular events that occur during limb development are also present in other embryonic regions; in this way, knowledge acquired from the analysis of limb formation can be used to interpret developmental processes elsewhere. The vertebrate limb originates as a small bud of undifferentiated mesenchymal cells covered by an ectodermal cap, which protrudes from the embryonic trunk. How this group of cells begins to proliferate and starts taking shape into a highly organized structure has long been the subject of research among dev elopmental biologists. Over the past years, grafting experiments on avian and amphibian models, combined with over-expression studies performed in chick and null mutant analysis in the mouse, have contributed to elucidating some of the molecular pathways t hat pattern the limb. However, many questions concerning limb outgrowth initiation and the establishment and maintenance of the signalling centres patterning the limb bud still remain unsolved. More recently, the zebra fish has become a third important model organisms for limb development, since its paired fins are homologous to tetrapod limbs. The development of novel tools, enabling the combination of both gain- and loss-of-function approaches including genetic and embryological manipulation of the embryo and the generation of large scale mutagenesis makes the zebra fish an attractive model system for limb development. Using the zebra fish, this project aims to gain further insight into the signalling cascades leading to limb initiation. In addition, mapping and characterization of an ENU induced limb mutant fish strain and an expression-based screen are going to be carried out to find novel genes involved in limb outgrowth.
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