A spatial atlas of Wnt receptors in adult mouse liver.

Hepatic zonation is critical for most metabolic functions in liver. Wnt signaling plays an important role in establishing and maintaining liver zonation. Yet, the anatomic expression of Wnt signaling components, especially all 10 Frizzled receptors (Fzds), has not been characterized in adult liver. To address this, we quantitatively mapped the spatial expression of Fzd receptors in adult mouse liver via multiplex fluorescent in situ hybridization. While all 10 Fzds are expressed within a metabolic unit, Fzds 1, 4, and 6 are the highest expressed. Though the majority of Wnt signaling occurs in Zone 3, expression of most Fzds is not zonated. In contrast, Fzd6 is preferentially expressed in Zone 1. We also verified that Wnt2 and Wnt9b expression is highly zonated and primarily found in Zone 3. Therefore, our results suggest that zonated Wnt/β-catenin signaling at baseline is mostly due to Wnt2 and Wnt9b rather than zonation of Fzd mRNA expression. Finally, we showed that Fzds and Wnts are not uniformly expressed by all hepatic cell types. Instead, there is broad distribution among both hepatocytes and non-parenchymal cells, including endothelial cells. Overall, our establishment of a definitive mRNA expression atlas, especially of Fzds, opens the door to future functional characterization in healthy and disease liver states.