A mutagenesis screen to identify novel genes required for late developmental processes in Xenopus tropicalis
Zusammenfassung der Projektergebnisse
The most prevalent human birth defects are those in cardiogenesis. Even for adults, heart defects contribute most to mortality in the western world. Since the current understanding of the genes involved in heart development is limited, a better understanding of the genetic pathways will open new treatments and thus lower mortality due to heart defects and disease. As the transcriptional networks regulating heart development are highly conserved between all organisms, genetic screening in the frog Xenopus tropicalis as a model organism is an excellent strategy to enable identification of novel genes. In previous work using random mutagenesis, we identified the mutant curly, which exhibits a developmental defect of the heart. In particular, very early heart development in curly-/- mutants appears normal, but during late linear heart tube formation the endocardium fails to line the myocardium and remains aggregated in the center of the forming heart tube. These mutant hearts also fail to loop. curly-/- mutants also show impaired expression of lymphatic marker genes and a disrupted vascular network, which may be an independent phenotype, or secondary to the primary defect in heart formation. Genetic mapping has positioned this mutation on Chromosome 4 Scaffold1:103722000-103826000. This region defines a physical distance of 105 kb containing 2 described and 1 unannotated genes that are conserved in mammals (Joint Genome Institute). In situ hybridization and RT PCR with subsequent sequencing showed that one of the three genes, pteg, is downregulated and misspliced in curly mutants. However, that pteg is indeed responsible for the curly phenotype could not be completed.
