Phillips, Helen MPapoutsi, TaniaSoenen, HelenaYbot-Gonzalez, PatriciaHenderson, Deborah JChaudhry, Bill2013-03-132013-03-132012-05-21Phillips HM, Papoutsi T, Soenen H, Ybot-Gonzalez P, Henderson DJ, Chaudhry B. Neural crest cell survival is dependent on Rho kinase and is required for development of the mid face in mouse embryos. PLoS ONE; 7(5):e37685http://hdl.handle.net/10668/830Journal Article; Research Support, Non-U.S. Gov't;Neural crest cells (NCC) give rise to much of the tissue that forms the vertebrate head and face, including cartilage and bone, cranial ganglia and teeth. In this study we show that conditional expression of a dominant-negative (DN) form of Rho kinase (Rock) in mouse NCC results in severe hypoplasia of the frontonasal processes and first pharyngeal arch, ultimately resulting in reduction of the maxilla and nasal bones and severe craniofacial clefting affecting the nose, palate and lip. These defects resemble frontonasal dysplasia in humans. Disruption of the actin cytoskeleton, which leads to abnormalities in cell-matrix attachment, is seen in the RockDN;Wnt1-cre mutant embryos. This leads to elevated cell death, resulting in NCC deficiency and hypoplastic NCC-derived craniofacial structures. Rock is thus essential for survival of NCC that form the craniofacial region. We propose that reduced NCC numbers in the frontonasal processes and first pharyngeal arch, resulting from exacerbated cell death, may be the common mechanism underlying frontonasal dysplasia.enCresta NeuralQuinasas Asociadas a rhoApoptosisActinasMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::ApoptosisMedical Subject Headings::Anatomy::Embryonic Structures::Branchial RegionMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell SurvivalMedical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital AbnormalitiesMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::CytoskeletonMedical Subject Headings::Anatomy::Body Regions::Head::FaceMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, TransgenicMedical Subject Headings::Anatomy::Embryonic Structures::Neural CrestMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::rho-Associated KinasesMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Microfilament Proteins::Actinsresearch article22629443open access10.1371/journal.pone.00376851932-6203PMC3357402