Non‐canonical Wnt Signaling in Embryonic Liver Development

Abstract

In addition to activating canonical beta‐catenin mediated signaling events, Wnt proteins also initiate beta‐catenin‐independent, non‐canonical signaling pathways: the planar cell polarity and Wnt/Ca2+ pathways. The planar cell polarity pathway promotes asymmetric cytoskeletal organization to establish cellular as well as tissue polarity in developing organs. Activation of the Wnt/Ca2+ pathway triggers release of intracellular calcium stores which activate signaling molecules and transcription factors and is critical for axis establishment and cell migration in embryos. These pathways play roles in the development of multiple tissues, but their contribution to liver development remains unexplored. We have investigated the expression by qPCR of the non‐canonical Frizzleds (Fz3, 4, 6) as well as their Wnt ligands (Wnts 4, 5a, 6, 7a and 11) at embryonic stages E12.5, E14.5, E16.5, E17.5, E18.5 and found a marked increase in Wnt5a expression in late liver development, peaking at E17.5. Consistent with activation of the Wnt/Ca2+ pathway, we have also seen an increase in Wnt5a protein as well as active CamKII by western blot, though we do not observe NFAT localization in nuclei coinciding with Wnt 5a. In summary, non‐canonical Wnt signaling may be playing an important role in late embryonic liver development.