title: Junctional neurulation: a unique developmental program shaping a discrete region of the spinal cord highly susceptible to neural tube defects.
abstract: In higher vertebrates, the primordium of the nervous system, the neural tube, is shaped along the rostrocaudal axis through two consecutive, radically different processes referred to as primary and secondary neurulation. Failures in neurulation lead to severe anomalies of the nervous system, called neural tube defects (NTDs), which are among the most common congenital malformations in humans. Mechanisms causing NTDs in humans remain ill-defined. Of particular interest, the thoracolumbar region, which encompasses many NTD cases in the spine, corresponds to the junction between primary and secondary neurulations. Elucidating which developmental processes operate during neurulation in this region is therefore pivotal to unraveling the etiology of NTDs. Here, using the chick embryo as a model, we show that, at the junction, the neural tube is elaborated by a unique developmental program involving concerted movements of elevation and folding combined with local cell ingression and accretion. This process ensures the topological continuity between the primary and secondary neural tubes while supplying all neural progenitors of both the junctional and secondary neural tubes. Because it is distinct from the other neurulation events, we term this phenomenon junctional neurulation. Moreover, the planar-cell-polarity member, Prickle-1, is recruited specifically during junctional neurulation and its misexpression within a limited time period suffices to cause anomalies that phenocopy lower spine NTDs in human. Our study thus provides a molecular and cellular basis for understanding the causality of NTD prevalence in humans and ascribes to Prickle-1 a critical role in lower spinal cord formation.
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Laboratoire de Biologie du Développement, 75005 Paris, France, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement, 75005 Paris, France, jean-loup.duband@upmc.fr alwyn.dady@gmail.com.
authors.forename: Alwyn
authors.initials: A
authors.lastname: Dady
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Laboratoire de Biologie du Développement, 75005 Paris, France, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement, 75005 Paris, France.
authors.forename: Emmanuelle
authors.identifier: http://orcid.org/0000-0001-5634-3174
authors.initials: E
authors.lastname: Havis
authors.affiliation: Unité de Technologies Chimiques et Biologiques pour la Santé, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8258, Institut National de la Santé et de la Recherche Médicale U1022, Université Paris Descartes, Faculté de Pharmacie, 75006 Paris, France, and.
authors.forename: Virginie
authors.initials: V
authors.lastname: Escriou
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Laboratoire de Biologie du Développement, 75005 Paris, France, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement, 75005 Paris, France, Assistance Publique-Hopitaux de Paris, Federation of Neurology, Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Catala
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Laboratoire de Biologie du Développement, 75005 Paris, France, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement, 75005 Paris, France, jean-loup.duband@upmc.fr alwyn.dady@gmail.com.
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Duband
mesh_terms: D000818:Animals; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism; D054259:Neural Tube / Q000196:embryology / Q000378:metabolism; D009436:Neural Tube Defects / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D054261:Neurulation; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D060588:LIM Domain Proteins; C515173:PRICKLE1 protein, human; D025521:Tumor Suppressor Proteins
keywords: Prickle-1; chick embryo; neural tube defects; neurulation