Peer-Reviewed Journal Details
Mandatory Fields
Liu, M,Guan, ZL,Shen, Q,Lalor, P,Fitzgerald, U,O'Brien, T,Dockery, P,Shen, SB
2016
July
Journal Of Neuroscience
Ulk4 Is Essential for Ciliogenesis and CSF Flow
Published
()
Optional Fields
ciliogenesis CSF hydrocephalus hypomorph mouse neurodevelopmental disorder Ulk4 PLANAR CELL POLARITY NEONATAL HYDROCEPHALUS CILIA FUNCTION MOTILE CILIA GENOME-WIDE MOUSE GENE EXPRESSION DEFECTS SCHIZOPHRENIA
36
7589
7600
Ciliopathies 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.
10.1523/JNEUROSCI.0621-16.2016
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