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dc.contributor.authorLiu, Min
dc.contributor.authorGuan, Zhenlong
dc.contributor.authorShen, Qin
dc.contributor.authorFlinter, Frances
dc.contributor.authorDomínguez, Laura
dc.contributor.authorAhn, Joo Wook
dc.contributor.authorCollier, David A.
dc.contributor.authorO'Brien, Timothy
dc.contributor.authorShen, Sanbing
dc.date.accessioned2018-09-20T16:14:43Z
dc.date.available2018-09-20T16:14:43Z
dc.date.issued2016-06-27
dc.identifier.citationLiu, Min; Guan, Zhenlong; Shen, Qin; Flinter, Frances; Domínguez, Laura; Ahn, Joo Wook; Collier, David A. O'Brien, Timothy; Shen, Sanbing (2016). Ulk4regulates neural stem cell pool. STEM CELLS 34 (9), 2318-2331
dc.identifier.issn1066-5099
dc.identifier.urihttp://hdl.handle.net/10379/12470
dc.description.abstractThe 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.
dc.publisherWiley-Blackwell
dc.relation.ispartofSTEM CELLS
dc.subjectcell cycle
dc.subjectcopy number variations
dc.subjectneural progenitor
dc.subjectneural stem cells
dc.subjectneurogenesis
dc.subjectrna sequencing
dc.subjectulk4
dc.subjectwnt signaling
dc.subjectautism spectrum disorders
dc.subjectde-novo mutations
dc.subjectbehavioral phenotypes
dc.subjectdevelopmental delay
dc.subjectsubventricular zone
dc.subjectschizophrenia
dc.subjectgene
dc.subjectproliferation
dc.subjectmouse
dc.subjectpathway
dc.titleUlk4regulates neural stem cell pool
dc.typeArticle
dc.identifier.doi10.1002/stem.2423
dc.local.publishedsourcehttps://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/stem.2423
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