Prostaglandin E2 (
PGE2) is a
lipid signaling molecule important for brain development and function. Various genetic and environmental factors can influence the level of
PGE2 and increase the risk of developing
Autism Spectrum Disorder (ASD). We have previously shown that in neuronal cell lines and mouse brain,
PGE2 can interfere with the Wnt canonical pathway, which is essential during early brain development. Higher levels of
PGE2 increased Wnt-dependent motility and proliferation of neuroectodermal stem cells, and modified the expression of Wnt genes previously linked to
autism disorders. We also recently established a cross-talk between these two pathways in the prenatal mouse brain lacking
PGE2 producing
enzyme (COX-/-). The current study complements the published data and reveals that
PGE2 signaling also converges with the Wnt canonical pathway in the developing mouse brain after maternal exposure to
PGE2 at the onset of neurogenesis. We found significant changes in the expression level of Wnt-target genes, Mmp7, Wnt2, and Wnt3a, during prenatal and early postnatal stages. Interestingly, we observed variability in the expression level of these genes between genetically-identical pups within the same pregnancy. Furthermore, we found that all the affected genes have been previously associated with disorders of the central nervous system, including
autism. We determined that prenatal exposure to
PGE2 affects the Wnt pathway at the level of β-
catenin, the major downstream regulator of Wnt-dependent gene transcription. We discuss how these results add new knowledge into the molecular mechanisms by which
PGE2 may interfere with neuronal development during critical periods.