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

ABSTRACT: Susceptible genetic polymorphisms and altered expression levels of protein kinase C (PKC)-encoding genes suggest overactivation of PKC in autism spectrum disorder (ASD) development. To delineate the pathological role of PKC, we pharmacologically stimulated its activity during the early development of zebrafish. Results demonstrated that PKC 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 PKC hyper-activation was furthe

SUBMITTER: Liu T 

PROVIDER: S-EPMC6199330 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature