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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2014     Display Documents



ID: 682206.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2014
ArhGEF18 regulates RhoA-Rock2 signaling to maintain neuro-epithelial apico-basal polarity and proliferation
Authors:Herder, C.; Swiercz, J. M.; Muller, C.; Peravali, R.; Quiring, R.; Offermanns, S.; Wittbrodt, J.; Loosli, F.
Date of Publication (YYYY-MM-DD):2013-07
Journal Abbrev.:Development
Volume:140
Issue / Number:13
Start Page:2787
End Page:2797
Audience:Not Specified
Abstract / Description:The vertebrate central nervous system develops from an epithelium where cells are polarized along the apicobasal axis. Loss of this polarity results in abnormal organ architecture, morphology and proliferation. We found that mutations of the guanine nucleotide exchange factor ArhGEF18 affect apicobasal polarity of the retinal neuroepithelium in medaka fish. We show that ArhGEF18-mediated activation of the small GTPase RhoA is required to maintain apicobasal polarity at the onset of retinal differentiation and to control the ratio of neurogenic to proliferative cell divisions. RhoA signals through Rock2 to regulate apicobasal polarity, tight junction localization and the cortical actin cytoskeleton. The human ArhGEF18 homologue can rescue the mutant phenotype, suggesting a conserved function in vertebrate neuroepithelia. Our analysis identifies ArhGEF18 as a key regulator of tissue architecture and function, controlling apicobasal polarity and proliferation through RhoA activation. We thus identify the control of neuroepithelial apicobasal polarity as a novel role for RhoA signaling in vertebrate development.
Free Keywords:Animals; Cell Differentiation/genetics/physiology; Cell Polarity/genetics/physiology; Guanine Nucleotide Exchange Factors/genetics/*metabolism; Oryzias/*embryology/*metabolism; Signal Transduction/genetics/physiology; rho-Associated Kinases/genetics/*metabolism; rhoA GTP-Binding Protein/genetics/*metabolism
External Publication Status:published
Document Type:Article
Communicated by:Svea Hümmer
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1477-9129 (Electronic) 0950-1991 (Linking) %R 10.1242/dev.096487
URL:http://www.ncbi.nlm.nih.gov/pubmed/23698346
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