A12N previously revealed links between epithelial cell-cell adhesion, cell polarity and mechanochemical signaling. Within the CRC1027 we will now explore how direct micro-environmental factors such as adhesion, biomechanical properties and spatial constraints control the differentiation of melanocytes and how alterations in these entities contribute to hypopigmentation and malignant disease. By combining functionalized surfaces and defined adhesion geometries with quantitative analysis of cell mechanics, loss-of-function models for polarity regulators and various reporter systems, we aim to delineate signaling pathways that link control of cell adhesion, shape and differentiation in this neural-crest derived cell lineage.