title: Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation.
abstract: The organization of neural progenitors in the developing mammalian neuroepithelium is marked by cadherin-based adherens junctions. Whereas RhoA, a founding member of the small Rho GTPase family, has been shown to play important roles in epithelial adherens junctions, its physiological roles in neural development remain uncertain due to the lack of specific loss-of-function studies. Here, we show that RhoA protein accumulates at adherens junctions in the developing mouse brain and colocalizes to the cadherin-catenin complex. Conditional deletion of RhoA in midbrain and forebrain neural progenitors using Wnt1-Cre and Foxg1-Cre mice, respectively, disrupts apical adherens junctions and causes massive dysplasia of the brain. Furthermore, RhoA-deficient neural progenitor cells exhibit accelerated proliferation, reduction of cell- cycle exit, and increased expression of downstream target genes of the hedgehog pathway. Consequently, both lines of conditional RhoA-deficient embryos exhibit expansion of neural progenitor cells and exencephaly-like protrusions. These results demonstrate a critical role of RhoA in the maintenance of apical adherens junctions and the regulation of neural progenitor proliferation in the developing mammalian brain.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Katayama
authors.forename: Jaime
authors.initials: J
authors.lastname: Melendez
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Baumann
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Leslie
authors.forename: Bharesh K
authors.initials: BK
authors.lastname: Chauhan
authors.forename: Niza
authors.initials: N
authors.lastname: Nemkul
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lang
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Kuan
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshida
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000196:embryology*; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007211:Indoles; D051379:Mice; D008817:Mice, Mutant Strains; D018613:Microscopy, Confocal; D058953:Neural Stem Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020742:rhoA GTP-Binding Protein / Q000172:deficiency* / Q000378:metabolism
chemical_list: D007211:Indoles; C007293:DAPI; D020742:rhoA GTP-Binding Protein; D001973:Bromodeoxyuridine