Work

Multifaceted role of Iroquois signaling in development and diseases

Year: 2025

Type: article

Abstract: The Iroquois ( Iro/Irx ) gene family encodes transcription factors that belong to the TALE-class homeodomain group, distinguished by a conserved Iro-box domain. Iroquois signaling is evolutionarily conserved from invertebrates to vertebrates and plays a vital role in embryonic development. In vertebrates Iro/Irx genes are control tissue compartmentalization, while in vertebrates they regulate gastrulation, neural patterning, and organogenesis. These genes are typically organized in conserved genomic clusters under shared regulatory control, reflecting their coordinated expression and common evolutionary origins. Beyond development, dysregulation of Iroquois genes has been implicated in diverse human diseases. Irx genes are increasingly linked with congenital disorders including congenital heart disease and neurodevelopmental abnormalities. Moreover, their emerging role in cancer biology has reveal context-dependent behavior, functioning as either tumor suppressors or oncogenes. Recent findings also highlighted their potential as clinical biomarkers in neurological and neoplastic diseases. Given their broad developmental and pathological roles, Iroquois genes are gaining recognition as promising candidates for therapeutic targeting and molecular diagnostics. This review integrates their developmental functions with their disease association to provide a comprehensive overview of the biological and clinical significance of Iroquois signaling. • Iroquois (Irx) genes encode conserved TALE-class transcription factors in metazoans. • Irx clusters (IrxA, IrxB) exhibit strong synteny and coordinated developmental expression. • They regulate neurogenesis, cardiogenesis, and organ patterning across vertebrate models. • Dysregulated Irx activity causes congenital heart and neurodevelopmental disorders. • In cancer, IRX1–6 act as tumor suppressors or oncogenes in a context-dependent manner. • Irx genes serve as potential biomarkers and therapeutic targets in human disease.

Source: Molecules and Cells

DOI: 10.1016/j.mocell.2025.100296