PIF2025 - Neuronal control of epithelial tissues: The role of sympathetic innervation in mammary gland homeostasis and breast cancer - (PID2024-162537OB-I00)

Tissue homeostasis and regeneration depend on precisely regulating stem and progenitor cell functions through specialized interactions with microenvironments (niche). Emerging evidence underscores the critical role of peripheral innervation in maintaining epithelial integrity and coordinating cellular responses to physiological and pathological stimuli. However, the systemic role of innervation in epithelial tissue biology is still poorly understood. This study aims to investigate the interaction between sympathetic innervation and the mammary gland as a model to explore the neuro-epithelial communication. We will address two key objectives using advanced lineage tracing and genetic models. First, we will examine the role of sympathetic innervation in mammary gland physiology, focusing on tissue maintenance, epithelial regeneration, and plasticity. Second, we will explore the influence of sympathetic innervation on breast cancer, particularly its role in tumor initiation and resistance to therapy. This research will provide essential insights into neuro-epithelial interactions and their impact on aging, degenerative diseases, and cancer progression by elucidating how neural signals regulate epithelial cell fate and plasticity. Our findings have the long-term potential to inform novel therapeutic strategies targeting neural regulation of epithelial tissues to enhance tissue regeneration and improve disease outcomes.