title: Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus.
abstract: Timely generation and normal maturation of ependymal cells along the aqueduct are critical for preventing physical blockage between the third and fourth ventricles and the development of fetal non-communicating hydrocephalus. Our study identifies Yap, the downstream effector of the evolutionarily conserved Hippo pathway, as a central regulator for generating developmentally controlled ependymal cells along the ventricular lining of the aqueduct. Yap function is necessary for proper proliferation of progenitors and apical attachment of ependymal precursor cells. Importantly, an injury signal initiated by lysophosphatidic acid (LPA), an upstream regulator of Yap that can cause fetal haemorrhagic hydrocephalus, deregulates Yap in the developing aqueduct. LPA exposure leads to the loss of N-cadherin concentrations at the apical endfeet, which can be partially restored by forced Yap expression and more efficiently by phosphomimetic Yap. These results reveal a novel function of Yap in retaining tissue junctions during normal development and after fetal brain injury.
authors.affiliation: Shriners Hospitals Pediatrics Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania 19140, USA.|Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Raehee
authors.initials: R
authors.lastname: Park
authors.affiliation: Shriners Hospitals Pediatrics Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania 19140, USA.|Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Uk Yeol
authors.initials: UY
authors.lastname: Moon
authors.affiliation: Shriners Hospitals Pediatrics Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania 19140, USA.|Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Shriners Hospitals Pediatrics Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania 19140, USA.|Graduate Program of Biomedical Sciences, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Lucinda J
authors.initials: LJ
authors.lastname: Hughes
authors.affiliation: Department of Cancer Biology, MD Anderson Cancer Research Center, University of Texas, Houston, Texas 77030, USA.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Johnson
authors.affiliation: Shriners Hospitals Pediatrics Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania 19140, USA.|Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Seo-Hee
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Shriners Hospitals Pediatrics Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania 19140, USA.|Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Seonhee
authors.initials: S
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002535:Cerebral Aqueduct / Q000378:metabolism* / Q000473:pathology; D004805:Ependyma / Q000378:metabolism* / Q000473:pathology; D005315:Fetal Diseases; D018507:Gene Expression Regulation, Developmental; D006849:Hydrocephalus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008246:Lysophospholipids / Q000633:toxicity; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; C489083:Cdh2 protein, mouse; D018797:Cell Cycle Proteins; D008246:Lysophospholipids; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C032881:lysophosphatidic acid