Cell-to-cell signaling is critical and indispensable in all multicellular organisms. Long-range signaling enables cells to communicate over several cell diameters is vital in development and homeostasis. If such signals are deployed at the wrong time and place, they lead to diseases, including cancers. Recent studies including ours revealed that cells communicate with direct contact through long, thin cellular protrusions. We are particularly interested in the mechanisms of cellular protrusion (referred to as airinemes or cytonemes)-mediated long-distance cell-cell communication between stem cells in zebrafish skin, human skin organoids cultures and disease contexts.