title: ArhGEF18 regulates RhoA-Rock2 signaling to maintain neuro-epithelial apico-basal polarity and proliferation.
abstract: 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.
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Hermann von Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Herder
authors.forename: Jakub M
authors.initials: JM
authors.lastname: Swiercz
authors.forename: Claudia
authors.initials: C
authors.lastname: Müller
authors.forename: Ravindra
authors.initials: R
authors.lastname: Peravali
authors.forename: Rebecca
authors.initials: R
authors.lastname: Quiring
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
authors.forename: Joachim
authors.initials: J
authors.lastname: Wittbrodt
authors.forename: Felix
authors.initials: F
authors.lastname: Loosli
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D009990:Oryzias / Q000196:embryology* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
keywords: ArhGEF18; Epithelial polarity; Medaka; Retina; Rho signaling; Teleost