CADHERIN EXPRESSION IN ZEBRAFISH WITH RETROGNATHIC JAW

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My project is to study jaw development in an animal model. The system we will work with in a group of zebrafish (Brachydanio rerio) mutants. These fish have a shortened life span due to feeding disabilities reminiscent of newborns with Pierre-Robin Syndrome. Zebrafish are an excellent model system for developmental studies since we can compare what is already known about the normal development of zebrafish with these mutants. One speculation is that cell-cell adhesion molecules, in particular cadherins, are important for morphogenesis in the zebrafish as in other organisms where they have been studied. The cadherins are a family of CA2+- dependent proteins which are essential for embryonic development. Currently, at least two dozen different cadherins have been described. The best characterized of these are E-cadherin (epithelial cadherin), N-cadherin (neural cadherin) P-cadherin (placental cadherin), and L-CAM (live cell adhesion molecule). The most conserved region of the proteins is the cytoplasmic domain. Our first goal in this project is to develop reagents to study cadherin expression during zebrafish development. For immunohistological and biochemical studies we are making antibodies against the conserved cytoplasmic region of the cadherins. For in situ hybridization studies we have made oligonucleotide primers based on the conserved region of the cadherins. We will use these primers to obtain zebrafish cadherin cDNA. Once we have confirmed the specificities of these reagents, we will use them to compare cadherin expression during development of the normal and mutant fish. KEYWORDS: cadherins, zebrafish, retrognathic lower jaw