Characterisation of chordal, a candidate gene for the Danforth`s short tail mutation

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The long-term objective of this project is to understand the mode of action of genes controlling notochord development. The notochord is an essential signalling centre for patterning of the paraxial mesoderm and neural tube. Consequently, perturbed notochord development leads to malformations or agenesis of the axial skeleton and defects of the spinal cord. Whereas the functions of the notochord are well established, little is known about the genes that control its developmental and integrity. The analysis of mutations specifically affecting notochord development and integrity is the key to identify such genes. This proposal focuses on the molecular genetic analysis of chordal, a candidate gene for Sd, which we isolated in our preliminary studies. The Danforth`s short tail (Sd) mutation affects notochord formation from the tail bud, and leads to the complete desintegration of the notochord along its entire length, indicating that the affected gene is essential for notochord development and maintenance. The goals of this proposal are to characterise chordal and its function in vitro and in vivo, and to test the hypothesis that chordal is the gene affected by the Sd mutation. This will be achieved by characterisation of the chordal gene and its transcripts, and its expression during normal embryogenesis and in adult tissues, and in Sd mutant embryos, characterisation of the CHORDAL protein(s) their biochemical properties and interacting partners, and by generating loss of function alleles of chordal. Together, the results of this study can be expected to elucidate the functions of a novel gene likely to be essential for notochord development and further our understanding of the molecular mechanisms controlling notochord development and integrity.