AUTHOR=Hu Ling , Chen Yi , Yang Cui-Ping , Huang Ying , Song Ning-Ning , Chen Jia-Yin , Sun Yu-Ling , Ding Yu-Qiang , Lang Bing TITLE=Ulk4, a Newly Discovered Susceptibility Gene for Schizophrenia, Regulates Corticogenesis in Mice JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.645368 DOI=10.3389/fcell.2021.645368 ISSN=2296-634X ABSTRACT=

Schizophrenia (SCZ) is a chronic and severe mental disease that affects around 1% of the population. The precise etiology of SCZ still remains largely unknown, and no conclusive mechanisms are firmly established. Recent advances in epidemiological and clinical investigation support an overwhelmingly strong neurodevelopmental origin for SCZ. Here, we demonstrated that Unc-51-like kinase 4 (Ulk4), a novel risk factor for major mental disorders including schizophrenia, is involved in the corticogenesis. Deletion of Ulk4 in mice led to significantly thinner layers of II–III, and V in the cerebral cortex, which was confirmed in conditional Ulk4 deletion mice achieved by Cre-loxp strategy. This abnormality might be caused by decreased intermediate neural progenitors and increased apoptosis. Thus, our data suggest that Ulk4 manipulates the behaviors of neural progenitors during brain development and, when functionally defective, leads to the reduction of specific cortical layers. This anomaly may increase predisposition to a range of neurodevelopmental disorders, including SCZ.