Developmental protein kinase C hyper-activation results in microcephaly and behavioral abnormalities in zebrafish.

Susceptible genetic polymorphisms and altered expression levels of protein kinase C genes suggest overactivation of in autism spectrum disorder (ASD) development. To delineate the pathological role of we pharmacologically stimulated its activity during the early development of zebrafish. Results demonstrated that duanyu1531 hyper-activation perturbs zebrafish development and induces a long-lasting head size deficit. The anatomical and cellular analysis revealed reduced neural precursor proliferation and newborn neuron formation. β-Catenin that is essential for brain growth is dramatically degraded. Stabilization of β-catenin by gsk3β inhibition partially restores the head size deficit. In addition, the neuropathogenic effect of developmental duanyu1531 hyper-activation was further supported by the alterations in the behavioral domain including motor abnormalities, heightened stress reactivity and impaired habituation learning. Taken together, by causally connecting early-life duanyu1531 hyper-activation to these neuropathological traits and the impaired neurogenesis, these results suggest that duanyu1531 could be a critical pathway in ASD pathogenesis.

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