Peer-Reviewed Journal Details
Mandatory Fields
Liu, M;Guan, ZL;Shen, Q;Flinter, F;Dominguez, L;Ahn, JW;Collier, DA;O'Brien, T;Shen, SB
2016
September
Stem Cells (Dayton, Ohio)
Ulk4 Regulates Neural Stem Cell Pool
Published
Altmetric: 7WOS: 8 ()
Optional Fields
AUTISM SPECTRUM DISORDERS DE-NOVO MUTATIONS BEHAVIORAL PHENOTYPES DEVELOPMENTAL DELAY SUBVENTRICULAR ZONE SCHIZOPHRENIA GENE PROLIFERATION MOUSE PATHWAY
34
2318
2331
The size of neural stem cell (NSC) pool at birth determines the starting point of adult neurogenesis. Aberrant neurogenesis is associated with major mental illness, in which ULK4 is proposed as a rare risk factor. Little is known about factors regulating the NSC pool, or function of the ULK4. Here, we showed that Ulk4(tm1a/tm1a) mice displayed a dramatically reduced NSC pool at birth. Ulk4 was expressed in a cell cycle-dependent manner and peaked in G2/M phases. Targeted disruption of the Ulk4 perturbed mid-neurogenesis and significantly reduced cerebral cortex in postnatal mice. Pathway analyses of dysregulated genes in Ulk4(tm1a/tm1a) mice revealed Ulk4 as a key regulator of cell cycle and NSC proliferation, partially through regulation of the Wnt signaling. In addition, we identified hemizygous deletion of ULK4 gene in 1.2/1,000 patients with pleiotropic symptoms including severe language delay and learning difficulties. ULK4, therefore, may significantly contribute to neurodevelopmental, neuropsychiatric, and neurodegenerative disorders.
1066-5099
10.1002/stem.2423
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