title: The Nf2 tumor suppressor regulates cell-cell adhesion during tissue fusion.
abstract: Tissue fusion, the morphogenic process by which epithelial sheets are drawn together and sealed, has been extensively studied in Drosophila. However, there are unique features of mammalian tissue fusion that remain poorly understood. Notably, detachment and apoptosis occur at the leading front in mammals but not in invertebrates. We found that in the mouse embryo, expression of the Nf2 tumor suppressor, merlin, is dynamically regulated during tissue fusion: Nf2 expression is low at the leading front before fusion and high across the fused tissue bridge. Mosaic Nf2 mutants exhibit a global defect in tissue fusion characterized by ectopic detachment and increased detachment-induced apoptosis (anoikis). By contrast with core components of the junctional complex, we find that merlin is required specifically for the assembly but not the maintenance of the junctional complex. Our work reveals that regulation of Nf2 expression is a previously unrecognized means of controlling adhesion at the leading front, thereby ensuring successful tissue fusion.
authors.affiliation: Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: McLaughlin
authors.forename: Genevieve M
authors.initials: GM
authors.lastname: Kruger
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Slocum
authors.forename: Denise
authors.initials: D
authors.lastname: Crowley
authors.forename: Norman A
authors.initials: NA
authors.lastname: Michaud
authors.forename: Jennifer
authors.initials: J
authors.lastname: Huang
authors.forename: Margaret
authors.initials: M
authors.lastname: Magendantz
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D004848:Epithelium / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009024:Morphogenesis / Q000502:physiology*; D025581:Neurofibromin 2 / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D025581:Neurofibromin 2