Characterisation of the Wnt antagonists and their response to conditionally activated Wnt signalling in the developing mouse forebrain.

In the present work, the expression patterns of the Wnt antagonists of the Dickkopf (Dkk) family were characterized in the developing mouse forebrain. In situ hybridisation on sections from E12 embryos showed an expression of dkk2 in the thalamus and dkk3 in the cortical hem and thalamus. At later developmental stages (E15.5, E17.5, and P0), little or no expression of dkk1, dkk2, and dkk4 was found in the forebrain, while dkk3 expression was detected in the ventricular zone (VZ) of the lateral and III ventricles, cortical neurons, migrating cells of the primary and secondary dentate migration, and the neuroblastic layer of the eye. In the adult forebrain, dkk3 expression was detected in the lateral VZ, pyramidal neurons of the hippocampus, and cortical neurons. We also provide evidence indicating that only dkk1 and dkk4, along with two other Wnt antagonists axin2 and wif1, but not dkk2 and dkk3, are involved in a feedback mechanism to restrain Wnt signalling in transgenic mice carrying a conditional augmentation of beta-catenin in the forebrain.