Lymphatics-epicardial cross talk via Reelin controls cardiac growth.

Cardiac lymphatics regulate embryonic heart growth through a Reelin-dependent epicardial signaling pathway, influencing organ size during development.

• Why it matters: Understanding how organ size is precisely controlled is crucial for insights into congenital heart defects and regenerative medicine. The mechanisms linking lymphatic vasculature to cardiac growth remain poorly understood, limiting potential therapeutic strategies.
• What they did: Researchers used single-cell RNA sequencing and loss-of-function mouse models to identify a regulatory network involving cardiac lymphatics, the epicardium, Wt1, and Igf1 signaling that governs late-stage embryonic heart growth. They also employed gain-of-function experiments in human epicardial organoids to study Reelin's role.
• The result: Findings reveal that cardiac lymphatics act as a physiological quality control system for heart size, with Reelin promoting epicardial fate, which may mediate lymphatics' beneficial effects in adult cardiac repair.