Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia.
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.
Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai 200092, China.|School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, Scotland, United Kingdom.
Bing
B
Lang
Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai 200092, China.
Lei
L
Zhang
Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai 200092, China.|School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, Scotland, United Kingdom.
Guanyu
G
Jiang
Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai 200092, China.|School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, Scotland, United Kingdom.
Ling
L
Hu
Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai 200092, China.|School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, Scotland, United Kingdom.
Wei
W
Lan
School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, Scotland, United Kingdom.
Lei
L
Zhao
School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, Scotland, United Kingdom.
Irene
I
Hunter
Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai 200092, China.|School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, Scotland, United Kingdom.
Michal
M
Pruski
Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai 200092, China.
Ning-Ning
NN
Song
Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai 200092, China.
Ying
Y
Huang
Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai 200092, China.
Ling
L
Zhang
School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, Scotland, United Kingdom.
David
D
St Clair
School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, Scotland, United Kingdom.
Colin D
CD
McCaig
Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai 200092, China.
Yu-Qiang
YQ
Ding
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