Proceedings for Annual Meeting of The Japanese Pharmacological Society
Online ISSN : 2435-4953
WCP2018 (The 18th World Congress of Basic and Clinical Pharmacology)
Session ID : WCP2018_PO4-1-53
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Poster session
Protein kinase D2 (PRKD2) regulates embryonic neural development
Baba MasayukiKensuke MatsumuraTakanobu NakazawaKazuki NagayasuAtsushi KasaiKazuhiro TakumaHitoshi Hashimoto
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CONFERENCE PROCEEDINGS OPEN ACCESS

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Abstract

Autism spectrum disorder (ASD), affecting approximately 1.5% of children, is a neurodevelopmental disorder characterized by deficits in social interaction and restricted and repetitive behaviors. Although molecular genetic studies significantly contribute to our understanding of ASD, the molecular etiology underlying the pathological phenotypes of ASD remains largely unclear. Furthermore, there is no established pharmacological treatment for their core symptoms. Recent studies have suggested that a spontaneous de novo mutation, a new mutation appeared in a child that neither the parent carries, contributes to the risk of ASD and often produces large effects and that genes with recurrent de novo possible loss-of-function mutations are likely to play key roles in the etiology of this disorder. We and others have recently found that PRKD2 has ASD-associated de novo mutations. These de novo mutations in PRKD2 can be associated with ASD risk, however, the role of PRKD2 as well as the biological significance of the identified mutations in the central nervous system is not well understood. Here, we conducted the functional analysis of PRKD2 in neural development.

We found that PRKD2 was highly expressed in the developing mouse cerebral cortex during embryonic neurodevelopment. We also showed that a knockdown of PRKD2 significantly inhibited neurite outgrowth in mouse neuroblastoma Neuro2A cells. We then examined the effects of PRKD2 knockdown on neural development in vivo. Using in utero electroporation technique, we found that a knockdown of PRKD2 resulted in a neural migration defect, increased neural proliferation and decreased neural progenitor differentiation.

Our results indicate that PRKD2 regulates neural development in vitro and in vivo. Considering many ASD susceptibility gene products are likely to have important roles in neural development, further analysis of the function of the de novo mutations on PRKD2 and other ASD susceptibility genes in neural development will provide important clues to the molecular pathophysiology of ASD.

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