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dc.contributor.authorLiu, M.
dc.contributor.authorGuan, Z.
dc.contributor.authorShen, Q.
dc.contributor.authorLalor, P.
dc.contributor.authorFitzgerald, U.
dc.contributor.authorO'Brien, T.
dc.contributor.authorDockery, P.
dc.contributor.authorShen, S.
dc.date.accessioned2018-09-20T16:14:43Z
dc.date.available2018-09-20T16:14:43Z
dc.date.issued2016-07-20
dc.identifier.citationLiu, M. Guan, Z.; Shen, Q.; Lalor, P.; Fitzgerald, U.; O'Brien, T.; Dockery, P.; Shen, S. (2016). Ulk4 is essential for ciliogenesis and csf flow. Journal of Neuroscience 36 (29), 7589-7600
dc.identifier.issn0270-6474,1529-2401
dc.identifier.urihttp://hdl.handle.net/10379/12471
dc.description.abstractCiliopathies are an emerging class of devastating disorders with pleiotropic symptoms affecting both the central and peripheral systems and commonly associated with hydrocephalus. Even though ciliary components and three master transcriptional regulators have been identified, little is known about the signaling molecules involved. We previously identified a novel gene, Unc51-like-kinase 4 (ULK4), as a risk factor of neurodevelopmental disorders. Here we took multidisciplinary approaches and uncovered essential roles of Ulk4 in ciliogenesis. We show that Ulk4 is predominantly expressed in the ventricular system, and Ulk4(tm1a/tm1a) ependymal cells display reduced/disorganized cilia with abnormal axonemes. Ulk4(tm1a/tm1a) mice exhibit dysfunctional subcommissural organs, obstructive aqueducts, and impaired CSF flow. Mechanistically, we performed whole-genome RNA sequencing and discovered that Ulk4 regulates the Foxj1 pathway specifically and an array of other ciliogenesis molecules. This is the first evidence demonstrating that ULK4 plays a vital role in ciliogenesis and that deficiency of ULK4 can cause hydrocephalus and ciliopathy-related disorders.
dc.publisherSociety for Neuroscience
dc.relation.ispartofJournal of Neuroscience
dc.subjectciliogenesis
dc.subjectcsf
dc.subjecthydrocephalus
dc.subjecthypomorph mouse
dc.subjectneurodevelopmental disorder
dc.subjectulk4
dc.subjectplanar cell polarity
dc.subjectneonatal hydrocephalus
dc.subjectcilia function
dc.subjectmotile cilia
dc.subjectgenome-wide
dc.subjectmouse
dc.subjectgene
dc.subjectexpression
dc.subjectdefects
dc.subjectschizophrenia
dc.titleUlk4 is essential for ciliogenesis and csf flow
dc.typeArticle
dc.identifier.doi10.1523/jneurosci.0621-16.2016
dc.local.publishedsourcehttp://www.jneurosci.org/content/36/29/7589.full.pdf
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