Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia

Bing Lang, Lei Zhang, Guanyu Jiang, Ling Hu, Wei Lan, Lei Zhao, Irene Hunter, Michal Pruski, Ning-Ning Song, Ying Huang, Ling Zhang, David St Clair, Colin D. McCaig, Yu-Qiang Ding

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Abstract

Schizophrenia is a debilitating familial neuropsychiatric disorder which affects 1% of people worldwide. Although the heritability for schizophrenia approaches 80% only a small proportion of the overall genetic risk has been accounted for, and to date only a limited number of genetic loci have been definitively implicated. We have identified recently through genetic and in vitro functional studies, a novel serine/threonine kinase gene, unc-51-like kinase 4 (ULK4), as a rare risk factor for major mental disorders including schizophrenia. Now using the approach of in utero gene transfer we have discovered that Ulk4 plays a key modulatory role in corticogenesis. Knockdown of Ulk4 leads to significantly decreased cell proliferation in germinal zones and profound deficits in radial migration and neurite ramification. These abnormalities can be reversed successfully by Ulk4 gene supplementation. Ulk4 also regulated acetylation of α-tubulin, an important post-translational modification of microtubules. We conclude that Ulk4 plays an essential role in normal brain development and when defective, the risk of neurodevelopmental disorders such as schizophrenia is increased.
Original languageEnglish
Article number31126
Pages (from-to)1-14
Number of pages14
JournalScientific Reports
Volume6
Early online date27 Sep 2016
DOIs
Publication statusPublished - 27 Sep 2016

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    Lang, B., Zhang, L., Jiang, G., Hu, L., Lan, W., Zhao, L., Hunter, I., Pruski, M., Song, N-N., Huang, Y., Zhang, L., St Clair, D., McCaig, C. D., & Ding, Y-Q. (2016). Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia. Scientific Reports, 6, 1-14. [31126]. https://doi.org/10.1038/srep31126