Wnt7a overexpression delays beta-tubulin III expression in transgenic mouse embryos.

Wnt7a and HA-tagged Wnt7a have previously been shown to promote or delay neuronal differentiation respectively. In this study, we show that embryonic days 9.5 and 10.5 transgenic mouse embryos overexpressing Wnt7a specifically in nestin-positive neural stem/progenitor cells displayed a delay in neuronal differentiation, assayed by beta-tubulin III expression. Our results corroborate previous studies using HA-Wnt7a, and suggest a critical role for Wnt7a in control of neuronal progenitor maturation.

Increased Wnt levels in the neural tube impair the function of adherens junctions during neurulation.

Wnt7a has been reported to signal via the canonical pathway, but also in non-canonical pathways acting on the cytoskeleton. Since Wnt7a is expressed after neurulation, we set to investigate the effects of Wnt7a on brain regionalization. We engineered transgenic mouse embryos that, under control of the nestin second intron, overexpressed Wnt7a in neural stem/progenitor cells. Surprisingly, transgenic embryos failed to complete cranial neurulation due to reduced levels and an impaired distribution of actin microfilaments, beta-catenin, and N-cadherin at the neural tube adherens junctions. These transgenic embryos expressed high levels of Vangl2, an essential component of non-canonical Wnt signaling. In agreement with a disregulation of this pathway, aberrant spinal neurulation was detected in the transgenic embryos, revealing a novel function regulated by Wnts. Thus, our findings suggest that Wnt7a overexpression disrupts normal Wnt signaling in the neural tube, resulting in defective adherens junctions and neurulation.