The opportunities and challenges of using Drosophila to model human cardiac diseases

Abstract

The Drosophila heart tube seems simple, yet it has notable anatomic complexity and contains highly specialized structures. In fact, the development of the fly heart tube much resembles that of the earliest stages of mammalian heart development, and the molecular-genetic mechanisms driving these processes are highly conserved between flies and humans. Combined with the fly’s unmatched genetic tools and a wide variety of techniques to assay both structure and function in the living fly heart, these attributes have made Drosophila a valuable model system for studying human heart development and disease. This perspective focuses on the functional and physiological similarities between fly and human hearts. Further, it discusses current limitations in using the fly, as well as promising prospects to expand the capabilities of Drosophila as a research model for studying human cardiac diseases.

Drosophila as a Model to Understand Second Heart Field Development

“…Since 75% of human disease genes have fly orthologs [55], this conservation of genes allows Drosophila to not only serve as a model to elucidate the mechanisms of human development but also act as a model for human disease [56]. The short life cycle of flies, and the ready ability to manipulate gene expression in this system using RNAi [57], has made Drosophila an ideal organism to screen for candidate disease genes [58,59]. For example, Ekure et al performed the exome sequencing of 98 Nigerian children suffering from CHD and their unaffected parents.…”

Editorial: Stretch and the heart: mechanoelectrical coupling and arrhythmias

“…It has been known for decades that SR membranes have a high Cl − and K + conductance that act as counter ion channels in the SR membrane to facilitate calcium fluxes (Dulhunty et al, 1996).Using an emerging animal model for cardiac physiology, Zechini et al provide evidence that Piezo is an SR-resident channel with an important role in buffering mechanical stress in the Drosophila heart. The use of Drosophila in cardiac physiology is emerging and promising given its genetic tractability (Zhao et al, 2023). It remains to be investigated whether the same mechanism is present in mammals.…”