Multifaceted Roles of Drosophila Toll Receptors: Integrating Immunity, Development, and Beyond

The Drosophila melanogaster (fruit fly) genome encodes nine Toll receptor proteins (Toll-1 to Toll-9), which are involved in diverse biological processes, including innate immunity, tissue homeostasis, neural function, embryonic development, and cell competition. Among them, Toll-1 is the best characterized family member, with pivotal roles in embryonic dorsal–ventral patterning and antimicrobial defense. Beyond Toll-1, accumulating evidence highlights the functionality and diversity of the other eight Toll receptors in various biological processes, including neural differentiation, tissue morphogenesis, cell competition, and antitumor activity. Although the functions of these receptors are increasingly recognized, many remain poorly understood and appear to be more context-dependent. This review summarizes current knowledge on the specialized roles, regulatory mechanisms, and signaling pathways governed by the Drosophila Toll family receptors, emphasizing their evolutionary versatility and cross-talk between immunity and development. We also discuss unresolved questions, such as ligand specificity among non-canonical Toll receptors and the mechanisms underlying context-dependent signaling outcomes, proposing future directions to unravel the complexity of Toll-mediated biology in metazoans. By distinguishing established mechanisms from proposed functions, this review identifies key gaps in our understanding of Toll receptor specificity and functional diversification.