We propose a detailed analysis of two zebrafish mutants with craniofacial and heart defects. Our goal is to isolate and characterize the mutated genes that are crucial for vertebrate development. The immediate goal for these two years is to map and clone the mutations and perform an extensive analysis of mutant phenotypes using in situ hybridizations, histological analysis and transplantation experiments. We will attempt to positionally clone the mutated genes using modern molecular genetic tools and taking advantage of the powerful techniques of zebrafish genetics. If novel genes are thus identified, their mammalian homologues will then be sought by in silico screening of EST databases. Molecular characterization of the genes will be completed and we will micro-inject DNA to mutant embryos to rescue the phenotype. We hope that this work will ultimately lead to a better understanding of the molecular and cellular basis of congenital human diseases of craniofacial structures and valve malformations.