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The Wnt/β-catenin signaling governs anterior-posterior neural patterning during development. Current hPSC differentiation protocols utilize a GSK3 inhibitor to activate Wnt signaling to promote posterior neural fate specification. However, GSK3 is a pleiotropic kinase involved in multiple signaling pathways and since GSK3 inhibition occurs downstream in the signaling cascade, it bypasses potential opportunities for achieving specificity or regulation at the receptor level. Additionally, the specific roles of individual FZD receptors in anterior-posterior patterning are poorly understood. Here, we characterized the cell surface expression of FZD receptors in neural progenitor cells with different regional identity. Our data reveals unique upregulation of FZD5 expression in anterior neural progenitors, and the expression is downregulated as cells adopt a posterior fate. This spatial regulation of FZD expression constitutes a novel regulatory mechanism adjusting the levels of β-catenin signaling along the anterior-posterior axis and possibly contribute to midbrain-hindbrain boundary formation. Stimulation of Wnt/β-catenin signaling in hPSC with a tetravalent antibody, which selectively triggers FZD5 and LRP6 clustering, leads to midbrain progenitor differentiation and give rise to functional dopaminergic neurons in vitro and in vivo.