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Published on: November 6, 2017
Understanding Forkhead box class O function: lessons from Drosophila melanogaster
1Molecular Profiling Research Informatics, Merck Research Laboratories, Rahway, New Jersey 07065, USA. oscar_puig@merck.com
Abstract:
Drosophila melanogaster is one of the most widely used model organisms. About 77% of known human disease genes have an ortholog in Drosophila, and many of the cellular signaling pathways are common between fruit flies and mammals. For example, a key signaling pathway in the regulation of growth and metabolism, the insulin/insulin-like growth factor 1 signaling pathway, is well conserved between flies and humans. Downstream effectors of this pathway are the Forkhead box class O (FOXO) family of transcription factors, with four members in mammals and a single FOXO protein in Drosophila, dFOXO. Research in Drosophila has been critical to elucidate the molecular mechanisms by which FOXO transcription factors regulate insulin signaling. In this review, we summarize the studies leading to dFOXO identification and its characterization as a central regulator of metabolism, life span, cell cycle, growth, and stress resistance.
Insights
Drosophila melanogaster serves as a key model organism for understanding human disease genes. Research highlights the conserved insulin signaling pathway and the role of dFOXO in regulating metabolism and lifespan.
Area of Science:
- * Molecular biology
- * Genetics
- * Physiology
Background:
- * Drosophila melanogaster is a widely utilized model organism in biological research.
- * Significant conservation exists between human and Drosophila genes, particularly in cellular signaling pathways.
- * The insulin/insulin-like growth factor 1 signaling pathway is crucial for growth and metabolism and is conserved across species.
Purpose of the Study:
- * To review the identification and characterization of the Drosophila FOXO (dFOXO) transcription factor.
- * To elucidate the molecular mechanisms of FOXO-regulated insulin signaling.
- * To summarize dFOXO's role as a central regulator in various biological processes.
Main Methods:
- * Literature review of studies on dFOXO.
- * Analysis of conserved insulin signaling pathways.
- * Examination of dFOXO's regulatory functions.
Main Results:
- * dFOXO is the single ortholog of the mammalian Forkhead box class O (FOXO) family of transcription factors.
- * Drosophila research has been instrumental in understanding FOXO's role in insulin signaling.
- * dFOXO is identified as a key regulator of metabolism, lifespan, cell cycle, growth, and stress resistance.
Conclusions:
- * The study of dFOXO in Drosophila provides critical insights into fundamental biological processes.
- * Conserved pathways highlight the utility of Drosophila as a model for human physiology and disease.
- * dFOXO's multifaceted regulatory roles underscore its importance in cellular and organismal health.
