Across metazoans, animal body structures and tissues exist in robust patterns that arise seemingly out of stochasticity of a few early cells in the embryo. These patterns ensure proper tissue form and function during early embryogenesis, development, homeostasis, and regeneration. Fundamental questions are how these patterns are generated and maintained during tissue homeostasis and regeneration. Though fascinating scientists for generations, these ideas remain poorly understood. Today, it is apparent that the Wnt/β-catenin pathway plays a central role in tissue patterning. Wnt proteins are small diffusible morphogens which are essential for cell type specification and patterning of tissues. In this review, we highlight several mechanisms described where the spatial properties of Wnt/β-catenin signaling are controlled, allowing them to work in combination with other diffusible molecules to control tissue patterning. We discuss examples of this self-patterning behavior during development and adult tissues’ maintenance. The combination of new physiological culture systems, mathematical approaches, and synthetic biology will continue to fuel discoveries about how tissues are patterned. These insights are critical for understanding the intricate interplay of core patterning signals and how they become disrupted in disease.
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