Genetic sex of enteric neurons enables ovarian relaxin to gate maternal gut plasticity
Loading...
Date
2026
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Animals must align intestinal plasticity and feeding with reproductive state, yet the checkpointthat gates these adaptations is unknown. Here we show that an ovary-to-enteric-neuron axisgates the onset of maternal gut plasticity in Drosophila. Genetic sex establishes endocrinecompetence in a subset of enteric neurons via the sex determination pathway, enabling femalespecific expression of the relaxin-family receptor Lgr3. After mating, steroid signallingincreases Lgr3 receptor expression, priming these neurons for reproductive adaptation. Onceoocytes mature fully, follicle cells secrete the relaxin-like hormone dILP8, which activatesLgr3 to trigger gut enlargement and increased feeding. Disrupting the sex determinationpathway in enteric neurons, Lgr3, or ovarian dILP8 prevents gut enlargement and reducesfeeding. Thus, genetic sex establishes competence, steroid signalling primes it, and ovarianrelaxin triggers it, defining a maternal intestinal plasticity checkpoint that ensures gutadaptations initiate only once reproduction is underway and energy demands peak. Ourfindings delineate an ovary-to-enteric-neuron axis that couples reproductive state to maternalgut plasticity.