A mutagenesis screen to identify novel genes required for late developmental processes in Xenopus tropicalis

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Inherited defects in cardiogenesis are the main cause of human birth defects. In addition, abnormal adult hearts are the most common cause of disease and mortality in the western world. The current therapeutic modalities and an understanding of the genes involved in heart development are limited. A better understanding of the genetic pathways that affect heart development is required to advance treatment possibilities. Random mutagenesis is a powerful strategy that allows identification of novel genes responsible for developmental processes in vertebrates. As the transcriptional networks regulating heart development are highly conserved between all organisms, genetic screening in the frog Xenopus tropicalis is as a model organism is an excellent strategy to enable identification of novel genes. One mutant blimpy, that exhibits a developmental defect of the heart, is of particular interest. In blimpy-/- mutants the very early heart development 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. blimpy-/- 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 with its closest genetic markers at 0.5 centimorgans (cM) and 0.6 cM respectively. This region defines a physical distance of 600 kb containing 6 described and 7 unannotated genes that are conserved in mammals (Joint Genome Institute).