• heart disease

Findings in Drosophila have implicated the fly gene pygo in cardiac dysfunction. Dmel\pygo is orthologous to two human genes, PYGO1 and PYGO2. This gene family encodes key nuclear components of the Wnt signaling pathway. Classical loss-of-function alleles, RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\pygo.

Both human genes, Hsap\PYGO1 and Hsap\PYGO2, have been introduced into flies. For both, heterologous rescue (functional complementation) of Dmel\pygo lethal phenotype has been demonstrated.

Animals homozygous for loss-of-function alleles of Dmel\pygo die during the larval or pupal stages. Homozygous embryos derived from homozygous female germline clones exhibit a strong segment polarity phenotype (similar to the phenotype of wg loss-of-function mutations) and die during the embryo stage. Targeted knockdown of pygo in the heart results in abnormalities in the cardiac valves and cardiac arrhythmia phenotypes which progress with age. There is genetic evidence that the heart-specific functions of pygo may be independent of canonical Wnt signaling.

Physical and genetic interactions of Dmel\pygo have been described; see below and in the pygo gene report. For transgenic human constructs, fly transgenic constructs and classical alleles, detailed phenotypic descriptions can be found in the allele reports; allele reports can be accessed from the gene report or by clicking on the allele symbols in the Disease Ontology and Reagent tables below.

[updated Apr. 2018 by FlyBase; FBrf0222196]