title: Junctionally restricted RhoA activity is necessary for apical constriction during phase 2 inner ear placode invagination.
abstract: After induction, the inner ear is transformed from a superficially located otic placode into an epithelial vesicle embedded in the mesenchyme of the head. Invagination of this epithelium is biphasic: phase 1 involves the expansion of the basal aspect of the otic cells, and phase 2, the constriction of their apices. Apical constriction is important not only for otic invagination, but also the invagination of many other epithelia; however, its molecular basis is still poorly understood. Here we show that phase 2 otic morphogenesis, like phase 1 morphogenesis, results from the activation of myosin-II. However unlike the actin depolymerising activity observed basally, active myosin-II results in actomyosin contractility. Myosin-II activation is triggered by the accumulation of the planar cell polarity (PCP) core protein, Celsr1 in apical junctions (AJ). Apically polarized Celsr1 orients and recruits the Rho Guanine exchange factor (GEF) ArhGEF11 to apical junctions, thus restricting RhoA activity to the junctional membrane where it activates the Rho kinase ROCK. We suggest that myosin-II and RhoA activation results in actomyosin dependent constriction in an apically polarised manner driving otic epithelium invagination.
authors.affiliation: Lab for Sensory Development, RIKEN Center for Development Biology, Kobe, Japan.
authors.forename: Xiaorei
authors.initials: X
authors.lastname: Sai
authors.affiliation: Lab for Cellular Morphogenesis, RIKEN Center for Development Biology, Kobe, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.affiliation: Lab for Sensory Development, RIKEN Center for Development Biology, Kobe, Japan. Electronic address: raj-ladher@cdb.riken.jp.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Ladher
mesh_terms: D000818:Animals; D001381:Azepines; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002642:Chick Embryo; D007758:Ear, Inner / Q000196:embryology* / Q000378:metabolism; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006576:Heterocyclic Compounds, 4 or More Rings; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D009024:Morphogenesis / Q000502:physiology*; D009281:Naphthalenes; D010455:Peptides; D034622:RNA Interference; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D001381:Azepines; D015820:Cadherins; D006576:Heterocyclic Compounds, 4 or More Rings; D009281:Naphthalenes; D010455:Peptides; C070571:ML 7; C065738:MLCK peptide; C472645:blebbistatin; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
keywords: Inner ear; Invagination; Morphogenesis; Myosin-II; Placode; RhoA