title: LKB1 signaling in cephalic neural crest cells is essential for vertebrate head development.
abstract: Head development in vertebrates proceeds through a series of elaborate patterning mechanisms and cell-cell interactions involving cephalic neural crest cells (CNCC). These cells undergo extensive migration along stereotypical paths after their separation from the dorsal margins of the neural tube and they give rise to most of the craniofacial skeleton. Here, we report that the silencing of the LKB1 tumor suppressor affects the delamination of pre-migratory CNCC from the neural primordium as well as their polarization and survival, thus resulting in severe facial and brain defects. We further show that LKB1-mediated effects on the development of CNCC involve the sequential activation of the AMP-activated protein kinase (AMPK), the Rho-dependent kinase (ROCK) and the actin-based motor protein myosin II. Collectively, these results establish that the complex morphogenetic processes governing head formation critically depends on the activation of the LKB1 signaling network in CNCC.
authors.affiliation: Institut de Neurobiologie, Laboratoire Neurobiologie et Développement, CNRS-UPR3294, Avenue de la Terrasses, F-91198 Gif-sur-Yvette, France. Electronic address: Sophie.Creuzet@inaf.cnrs-gif.fr.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Creuzet
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France.
authors.forename: Jean P
authors.initials: JP
authors.lastname: Viallet
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Ghawitian
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France.
authors.forename: Sakina
authors.initials: S
authors.lastname: Torch
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Thélu
authors.affiliation: Institut de Neurobiologie, Laboratoire Neurobiologie et Développement, CNRS-UPR3294, Avenue de la Terrasses, F-91198 Gif-sur-Yvette, France.
authors.forename: Moussab
authors.initials: M
authors.lastname: Alrajeh
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France.
authors.forename: Anca G
authors.initials: AG
authors.lastname: Radu
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bouvard
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France.
authors.forename: Floriane
authors.initials: F
authors.lastname: Costagliola
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France.
authors.forename: Maïlys Le
authors.initials: ML
authors.lastname: Borgne
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Buchet-Poyau
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Aznar
authors.affiliation: Institut de Neurobiologie, Laboratoire Neurobiologie et Développement, CNRS-UPR3294, Avenue de la Terrasses, F-91198 Gif-sur-Yvette, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Buschlen
authors.affiliation: Department of Biological Science, Hiroshima University, Higashi-Hiroshima 739-8526, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoya
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France. Electronic address: chantal.thibert@univ-grenoble-alpes.fr.
authors.forename: Chantal
authors.initials: C
authors.lastname: Thibert
authors.affiliation: University Grenoble Alpes, IAB, F-38000 Grenoble, France; INSERM, IAB, F-38000 Grenoble, France. Electronic address: Marc.Billaud@ujf-grenoble.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Billaud
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology; D000818:Animals; D030161:Avian Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002642:Chick Embryo; D019465:Craniofacial Abnormalities / Q000196:embryology / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006257:Head / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D018994:Myosin Light Chains / Q000502:physiology; D009432:Neural Crest / Q000166:cytology / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D054460:rho-Associated Kinases / Q000502:physiology
chemical_list: D030161:Avian Proteins; D018994:Myosin Light Chains; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D054460:rho-Associated Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Actin dynamic; Cell polarity; Cephalic neural crest cells; Head development; Lkb1