Fig. 8: Synergistic effects of Vangl2 and PTK7 on neural tube closure depend on Vangl2 tyrosine phosphorylation.

Neural folding defects were assessed in embryos injected with RNAs encoding PTK7 and different forms of Vangl2 (200 pg each) into two dorsal animal blastomeres (inset in A, red arrows). Dorsal views of representative embryos exhibit no A, mild B or severe C disruption of neural tube closure. Co-injection of PTK7 and Y > F Vangl2 RNAs causes stronger neural tube defects (NTDs) compared to the co-injection of the wild type or Y > E Vangl2 RNAs. The degree of neural tube closure was scored at stage 17 by the distance between the opposing neural folds near the brain-spinal cord border (arrowheads), anterior is to the top. Dashed line marks the midline. D Quantification showing frequencies of normal neural folds A, as compared to mild B and severe C defects. The number of scored embryos is shown in the graph. Data represent two independent experiments. E Model. Graded FGF/FGFR1 activity triggers Vangl2 tyrosine phosphorylation at posterior cell edges, inhibiting the formation of Vangl2-Pk3 and Vangl2-PTK7 complexes, leading to reduced posterior accumulation of Vangl2. PTK7 is proposed to act as a feedback regulator and FGFR1 antagonist, promoting Vangl2 dephosphorylation through phosphatase (PPase) recruitment.